[Federal Register Volume 90, Number 172 (Tuesday, September 9, 2025)]
[Notices]
[Pages 43458-43460]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-17226]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2019-D-2102]
Development of Therapeutic Protein Biosimilars: Comparative
Analytical Assessment and Other Quality-Related Considerations;
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
``Development of Therapeutic Protein Biosimilars: Comparative
Analytical Assessment and Other Quality-Related Considerations.'' This
guidance describes the Agency's recommendations on the design and
evaluation of comparative analytical studies intended to support a
demonstration that a proposed therapeutic protein product is biosimilar
to a reference product licensed under the Public Health Service Act
(PHS Act). Additionally, this guidance is intended to provide
recommendations to sponsors on the scientific and technical information
for the chemistry, manufacturing, and controls (CMC) portion of a
marketing application for a proposed product submitted under the PHS
Act. This guidance finalizes and replaces the draft guidance of the
same title issued on May 22, 2019, and replaces the final guidance
``Quality Considerations in Demonstrating Biosimilarity of a
Therapeutic Protein Product to a Reference Product'' issued on April
30, 2015.
DATES: The announcement of the guidance is published in the Federal
Register on September 9, 2025.
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
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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-2019-D-2102 for ``Development of Therapeutic Protein Biosimilars:
Comparative Analytical Assessment and Other Quality-Related
Considerations.'' 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. 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: Mustafa Unlu, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 1139, Silver Spring, MD 20993, 301-796-
3396, [email protected]. 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 final guidance for industry
entitled ``Development of Therapeutic Protein Biosimilars: Comparative
Analytical Assessment and Other Quality-Related Considerations.'' This
final guidance describes the Agency's recommendations on the design and
evaluation of comparative analytical studies intended to support a
demonstration that a proposed therapeutic protein product is biosimilar
to a reference product licensed under section 351(a) of the PHS Act (42
U.S.C. 262(a)). Additionally, this final guidance is intended to
provide recommendations to sponsors on the scientific and technical
information for the CMC portion of a marketing application for a
proposed product submitted under section 351(k) of the PHS Act.
Although the 351(k) pathway applies generally to biological products,
this final guidance focuses on therapeutic protein products.
Section 351(k) of the PHS Act (42 U.S.C. 262(k)) provides an
abbreviated licensure pathway for biological products shown to be
biosimilar to or interchangeable with an FDA-licensed reference product
and sets forth the requirements for an application for a proposed
biosimilar product and an application for a proposed interchangeable
biosimilar product. Under this abbreviated licensure pathway, FDA will
license a proposed biological product submitted under section 351(k) of
the PHS Act if, among other things, FDA determines that the information
submitted in the application is sufficient to show that the biological
product is biosimilar to the reference product.
This guidance finalizes the draft guidance entitled ``Development
of Therapeutic Protein Biosimilars: Comparative Analytical Assessment
and Other Quality-Related Considerations'' issued on May 22, 2019 (84
FR 23569). FDA considered comments received on the draft guidance as
the guidance was finalized. Comments submitted to the docket of the
draft guidance addressed a range of issues, including clarifying
questions on reference product lots and on the analyses of the
comparative analytical data. FDA provided additional information and
clarifying edits in response to comments as appropriate. In addition,
editorial changes were made to improve clarity.
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 ``Development of Therapeutic Protein
Biosimilars: Comparative Analytical Assessment and Other Quality-
Related Considerations.'' 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. The
previously approved collections of information are subject to
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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 related to the submission of: (1) An investigational new
drug application under 21 CFR part 312 have been approved under OMB
control number 0910-0014; (2) a new drug application, under 21 CFR part
314 have been approved under OMB control number 0910-0001; (3) a
biologics license application (BLA) under 21 CFR part 601 have been
approved under OMB control number 0910-0338; and (4) a BLA under
section 351(k), under 21 CFR part 601 have been approved under OMB
control number 0910-0718. The collections of information regarding
current good manufacturing processes for drug products and biological
products under 21 CFR part 211 and 21 CFR parts 600, 601, and 610 have
been approved under OMB control numbers 0910-0139 and 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.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2025-17226 Filed 9-8-25; 8:45 am]
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