Notice2025-20380
Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies; Draft Guidance for Industry; Availability
Primary source
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Published
November 20, 2025
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a draft guidance for industry entitled "Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies." This draft guidance describes considerations regarding a comparative clinical study or studies with efficacy endpoints (a comparative efficacy study or CES) intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submitting a marketing application under the Public Health Service Act (PHS Act).
Full Text
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<title>Federal Register, Volume 90 Issue 222 (Thursday, November 20, 2025)</title>
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[Federal Register Volume 90, Number 222 (Thursday, November 20, 2025)]
[Notices]
[Pages 52410-52411]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-20380]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-D-0605]
Scientific Considerations in Demonstrating Biosimilarity to a
Reference Product: Updated Recommendations for Assessing the Need for
Comparative Efficacy Studies; Draft Guidance for Industry; Availability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, Agency, or we) is
announcing the availability of a draft guidance for industry entitled
``Scientific Considerations in Demonstrating Biosimilarity to a
Reference Product: Updated Recommendations for Assessing the Need for
Comparative Efficacy Studies.'' This draft guidance describes
considerations regarding a comparative clinical study or studies with
efficacy endpoints (a comparative efficacy study or CES) intended to
support a demonstration that a proposed therapeutic protein product is
biosimilar to a reference product for the purpose of submitting a
marketing application under the Public Health Service Act (PHS Act).
DATES: Submit either electronic or written comments on the draft
guidance by January 20, 2026 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:
<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 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-2011-D-0605 for ``Scientific Considerations in Demonstrating
Biosimilarity to a Reference Product: Updated Recommendations for
Assessing the Need for Comparative Efficacy Studies.'' Received
comments
[[Page 52411]]
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 the draft 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. Send one
self-addressed 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: Mustafa Unlu, Center for Drug
Evaluation and Research (HF-22), Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 22, Rm. 1139, Silver Spring, MD 20993-0001,
301-796-3396, <a href="/cdn-cgi/l/email-protection#a8c5dddbdcc9cec986ddc6c4dde8ceccc986c0c0db86cfc7de"><span class="__cf_email__" data-cfemail="ff928a8c8b9e999ed18a91938abf999b9ed197978cd1989089">[email protected]</span></a>; or Philip 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 ``Scientific Considerations in Demonstrating Biosimilarity to
a Reference Product: Updated Recommendations for Assessing the Need for
Comparative Efficacy Studies.'' The final guidance for industry
entitled ``Scientific Considerations in Demonstrating Biosimilarity to
a Reference product'' published in April 2015 (Scientific
Considerations Guidance) described general considerations for
comparative clinical studies intended to support a demonstration that a
proposed therapeutic protein product (proposed biosimilar or proposed
biosimilar product) is biosimilar to a reference product for the
purpose of submitting a marketing application under section 351(k) of
the PHS Act (42 U.S.C. 262(k)). Comparative clinical studies typically
have been designed to analyze and compare a clinical efficacy outcome
or other relevant therapeutic effect between the proposed product and
the reference product.
Since publication of the Scientific Considerations Guidance, FDA
has gained significant experience in evaluating analytical differences
between proposed biosimilar products and their reference products and
understanding the impact of those analytical differences on clinical
performance. A comparative analytical assessment is generally more
sensitive than a CES to detect differences between two products, should
any exist, that may preclude a demonstration of biosimilarity.
Accordingly, FDA's scientific approach to when a CES may not be
necessary to support a demonstration of biosimilarity is evolving. FDA
is now issuing this draft guidance to provide an overview of important
scientific considerations for determining when a CES may inform a
demonstration of biosimilarity. In the future, the Agency intends to
consolidate certain recommendations in a new guidance describing
scientific considerations in demonstrating biosimilarity to a reference
product.
This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). 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. We are specifically seeking comments on
potential cost savings for biosimilar development programs that use a
streamlined approach as described in this draft guidance.
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 (44 U.S.C. 3501-3521). The collections of information
relating to the submission of a biologics license application under
section 351(k) of the PHS Act, including the submission of data from
comparative analytical assessments and a clinical study or studies
(including the assessment of immunogenicity and pharmacokinetics or
pharmacodynamics) that are sufficient to demonstrate safety, purity,
and potency in one or more appropriate conditions of use for which the
reference product is licensed, have been approved under OMB control
number 0910-0718. The collections of information relating to formal
meetings between sponsors or applicants and FDA have been approved
under OMB control number 0910-0001.
III. Electronic Access
Persons with access to the internet may obtain the draft 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/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>, or <a href="https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</a>.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-20380 Filed 11-19-25; 8:45 am]
BILLING CODE 4164-01-P
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