[Federal Register Volume 87, Number 41 (Wednesday, March 2, 2022)]
[Notices]
[Pages 11720-11722]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-04397]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-2777]


Expansion Cohorts: Use in First-in-Human Clinical Trials To 
Expedite Development of Oncology Drugs and Biologics; 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 ``Expansion 
Cohorts: Use in First-in-Human 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finalizes the draft guidance of the same name issued in August 2018.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:
    <bullet> 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.
    <bullet> If you want to submit a comment with confidential 
information that you do not wish to be made available to the

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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:
    <bullet> 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.
    <bullet> 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.
    <bullet> 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-in-Human 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:
    <bullet> 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.
    <bullet> 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.
    <bullet> Language added to state that development of an age-
appropriate formulation may be necessary for pediatric populations.
    <bullet> 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

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(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 Sec. Sec.  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/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics, https://www.fda.gov/regulatory-information/search-fda-guidance-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