Notice2022-04397
Expansion Cohorts: Use in First-in-Human Clinical Trials To Expedite Development of Oncology Drugs and Biologics; Guidance for Industry; Availability
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Published
March 2, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
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 This guidance finalizes the draft guidance of the same name issued in August 2018.
Full Text
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<title>Federal Register, Volume 87 Issue 41 (Wednesday, March 2, 2022)</title>
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[Federal Register Volume 87, Number 41 (Wednesday, March 2, 2022)]
[Notices]
[Pages 11720-11722]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[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finalizes the draft guidance of the same name issued in August 2018.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: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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 <a href="https://www.fda.gov/media/116754/download">https://www.fda.gov/media/116754/download</a>) 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 <a href="https://www.fda.gov/media/86377/download">https://www.fda.gov/media/86377/download</a>) 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 <a href="https://www.fda.gov/media/93884/download">https://www.fda.gov/media/93884/download</a>) 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 <a href="https://www.fda.gov/media/109951/download">https://www.fda.gov/media/109951/download</a>) 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 <a href="https://www.fda.gov/media/126910/download">https://www.fda.gov/media/126910/download</a>) have been approved under OMB control number
0910-0430.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
<a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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
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