[Federal Register Volume 90, Number 135 (Thursday, July 17, 2025)]
[Notices]
[Pages 33388-33389]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-13366]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2025-D-1071]
Development of Cancer Drugs for Use in Novel Combination--
Determining the Contribution of the Individual Drugs' Effects; Draft
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled
``Development of Cancer Drugs for Use in Novel Combination--Determining
the Contribution of the Individual Drugs' Effects.'' This draft
guidance is intended for sponsors developing drugs for use in
combination for the treatment of cancer and provides recommendations
for characterizing the safety and effectiveness of individual drugs for
use in a novel combination regimen in oncology (i.e., demonstrating the
contribution of each drug to the overall effect that is observed for
the population). This guidance expands on the recommendations in the
2013 guidance for industry entitled ``Codevelopment of Two or More New
Investigational Drugs for Use in Combination.'' This guidance does not
address contribution of effect in settings where an investigational
drug is being developed in combination with a drug approved for the
same indication for the purposes of comparing the approved drug to the
combination or to fixed combinations of previously approved drugs for
the approved indication(s).
DATES: Submit either electronic or written comments on the draft
guidance by September 15, 2025 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance.
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-2025-D-1071 for ``Development of Cancer Drugs for Use in Novel
Combination--Determining the Contribution of the Individual Drugs'
Effects.'' 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.
[[Page 33389]]
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 Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3103, 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: Donna Rivera, Oncology Center of
Excellence, Food and Drug Administration, [email protected]; or
Phillip Kurs, Center for Biologics Evaluation and Research, Food and
Drug Administration, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Development of Cancer Drugs for Use in Novel Combination--
Determining the Contribution of the Individual Drugs' Effects.'' This
draft guidance describes FDA's recommendations for characterizing the
safety and effectiveness of individual drugs for use in a novel
combination regimen (i.e., demonstrating the contribution of each drug
to the overall effect that is observed for the population) in treating
cancer, including use of data external to a trial for demonstration of
contribution of effect for the following types of novel combinations in
oncology: (1) two (or more) investigational drugs that have not been
previously approved by FDA for any indication; (2) an investigational
drug with a drug(s) approved for a different indication; or (3) two (or
more) drugs approved for a different indication(s). This guidance
expands on the recommendations in the 2013 guidance for industry
entitled ``Codevelopment of Two or More New Investigational Drugs for
Use in Combination.''
Combination therapy in oncology is an important treatment modality.
Scientific advances have increased our understanding of the
pathophysiological processes that underlie many cancers. This increased
understanding has provided further impetus to develop new therapeutic
approaches using combinations of drugs directed at multiple therapeutic
targets to improve treatment response, minimize adverse events, or
both. A novel combination of drugs may be considered for development
when the necessity of each drug in the proposed combination is
supported by a strong biologic rationale including the nonclinical
characterization of each drug in the combination and early clinical
evidence. A critical aspect of codevelopment of novel combinations of
oncology drugs is the characterization of the safety and effectiveness
of the individual drugs in the combination because the benefit of using
the individual drugs in combination is weighed against the added
toxicity when they are used together. In some cases, the conventional
approach to demonstrating contribution of effect by employing a
standard factorial design may be infeasible. Therefore, FDA is
providing recommendations regarding the use of external data for
demonstrating the contribution of the individual drugs to the effect of
a combination regimen and the key aspects to consider including
selection of data source(s) and endpoints, and suitability of a data
source.
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 ``Development
of Cancer Drugs for Use in Novel Combination--Determining the
Contribution of the Individual Drugs' Effects.'' 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.
As we develop final guidance on this topic, FDA will consider
comments on costs or cost savings the guidance may generate, relevant
for Executive Order 14192.
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 part 312 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; and the collections of
information in 21 CFR part 601 have been approved under OMB control
number 0910-0338.
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/biologics-guidances,
https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.
Dated: July 14, 2025.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-13366 Filed 7-16-25; 8:45 am]
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