Expansion Cohorts: Use in First-in-Human Clinical Trials To Expedite Development of Oncology Drugs and Biologics; Guidance for Industry; Availability, 11720-11722 [2022-04397]
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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-201509-18/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copies of the draft guidance to the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for electronic access to the draft
guidance document.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:
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.
I. Background
[FR Doc. 2022–04370 Filed 3–1–22; 8:45 am]
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
BILLING CODE 4164–01–P
VerDate Sep<11>2014
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Jkt 256001
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.
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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-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.
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:
SUMMARY:
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
E:\FR\FM\02MRN1.SGM
02MRN1
Federal Register / Vol. 87, No. 41 / Wednesday, March 2, 2022 / Notices
lotter on DSK11XQN23PROD with NOTICES1
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-201509-18/pdf/2015-23389.pdf.
VerDate Sep<11>2014
17:34 Mar 01, 2022
Jkt 256001
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
PO 00000
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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
E:\FR\FM\02MRN1.SGM
02MRN1
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
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17:34 Mar 01, 2022
Jkt 256001
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:
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
PO 00000
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Sfmt 4703
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
Notice of availability.
SUMMARY:
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:
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
E:\FR\FM\02MRN1.SGM
02MRN1
]]>Agencies
[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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:
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
[[Page 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-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:
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
[[Page 11722]]
(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
