Postapproval Manufacturing Changes to Biosimilar and Interchangeable Biosimilar Products: Questions and Answers; Guidance for Industry; Availability

Issuing agencies

Abstract

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled "Postapproval Manufacturing Changes to Biosimilar and Interchangeable Biosimilar Products: Questions and Answers." This guidance provides answers to commonly asked questions from applicants and other interested parties regarding postapproval manufacturing changes made to biosimilar and interchangeable biosimilar products licensed under the Public Health Service Act (PHS Act). This guidance finalizes the draft guidance of the same title issued on July 23, 2024.

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<title>Federal Register, Volume 91 Issue 196 (Tuesday, October 13, 2026)</title>
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[Federal Register Volume 91, Number 196 (Tuesday, October 13, 2026)]
[Notices]
[Pages 64931-64933]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-20817]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2024-D-2581]


Postapproval Manufacturing Changes to Biosimilar and 
Interchangeable Biosimilar Products: Questions and Answers; 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 
``Postapproval Manufacturing Changes to Biosimilar and Interchangeable 
Biosimilar Products: Questions and Answers.'' This guidance provides 
answers to commonly asked questions from applicants and other 
interested parties regarding postapproval manufacturing changes made to 
biosimilar and interchangeable biosimilar products licensed under the 
Public Health Service Act (PHS Act). This guidance finalizes the draft 
guidance of the same title issued on July 23, 2024.

DATES: The announcement of the guidance is published in the Federal 
Register October 13, 2026.

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 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-2024-D-2581 for ``Postapproval Manufacturing Changes to Biosimilar 
and Interchangeable Biosimilar Products: Questions and Answers.'' 
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

[[Page 64932]]

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. 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: Ashley Boam, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm 4192, Silver, Spring, MD 20993-0002, 301-
796-6341, <a href="/cdn-cgi/l/email-protection#bad9dedfc897cbcfdbd6d3cec397cad5d6d3d9c3fadcdedb94d2d2c994ddd5cc"><span class="__cf_email__" data-cfemail="87e4e3e2f5aaf6f2e6ebeef3feaaf7e8ebeee4fec7e1e3e6a9efeff4a9e0e8f1">[email&#160;protected]</span></a>; 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 guidance for industry 
entitled ``Postapproval Manufacturing Changes to Biosimilar and 
Interchangeable Biosimilar Products: Questions and Answers.'' This 
guidance provides answers to commonly asked questions from applicants 
and other interested parties regarding postapproval manufacturing 
changes (referred to as ``manufacturing changes'' throughout this 
notice) made to biosimilar and interchangeable biosimilar products 
licensed under section 351(k) of the PHS Act (42 U.S.C. 262(k)). FDA is 
publishing this guidance to fulfill the commitment made in the 2022 
reauthorization of the Biosimilar User Fee Act (BsUFA III, Title IV--
Fees Relating to Biosimilar Biological Products, Pub. L. 117-180) for 
fiscal years 2023 through 2027. This guidance is intended to inform 
applicants of the nature and type of information, for different 
reporting categories, that applicants should provide to support 
manufacturing changes to licensed biosimilar and licensed 
interchangeable biosimilar products. The recommendations in this 
guidance are intended to be consistent with the principles outlined in 
the International Council for Harmonisation (ICH) guidance for industry 
entitled ``Q5E Comparability of Biotechnological/Biological Products 
Subject to Changes in Their Manufacturing Process'' (June 2005) (ICH 
Q5E), available at <a href="https://www.fda.gov/media/71489/download">https://www.fda.gov/media/71489/download</a>.
    In the Federal Register of September 20, 2021 (86 FR 52154), FDA 
published the notice of availability of a guidance for industry 
entitled ``Questions and Answers on Biosimilar Development and the BPCI 
Act'' (``Q&A biosimilar development guidance''), available at <a href="https://www.fda.gov/media/119258/download">https://www.fda.gov/media/119258/download</a> (revised March 10, 2026; see 91 FR 
11555). The intent of that guidance is to provide answers to commonly 
asked questions from applicants and other interested parties to, among 
other things, facilitate the development of proposed biosimilar and 
proposed interchangeable biosimilar products under the Biologics Price 
Competition and Innovation Act of 2009. Postapproval manufacturing 
changes to biosimilar products is the subject of Q&A I.20 in the Q&A 
biosimilar development guidance. FDA did not provide recommendations 
for interchangeable biosimilar products in Q&A I.20 because FDA had 
limited experience regarding manufacturing changes for licensed 
interchangeable biosimilar products when that guidance originally 
issued. FDA has since determined that the principles that apply to 
manufacturing changes for biosimilar products are relevant to 
interchangeable biosimilar products. Recognizing that this discussion 
merits more exploration than a single Q&A item can facilitate, FDA has 
developed this guidance, which elaborates on the topic of manufacturing 
changes made to both licensed biosimilar and licensed interchangeable 
biosimilar products.
    FDA may withdraw a Q&A that was previously in a guidance if FDA 
determines that the issue described in the Q&A is addressed in another 
guidance. The finalization of this guidance reflects FDA's current 
thinking on the topic of postapproval manufacturing changes to 
biosimilar and interchangeable biosimilar products and supersedes the 
recommendations provided in Q&A I.20 in the Q&A biosimilar development 
guidance. Therefore, at this time, FDA is also withdrawing Q&A I.20 
from the Q&A biosimilar development guidance. Since this guidance is 
being issued as a standalone guidance, it does not retain the same 
numbering as the Q&A biosimilar development guidance.
    This guidance finalizes the draft guidance entitled ``Postapproval 
Manufacturing Changes to Biosimilar and Interchangeable Biosimilar 
Products: Questions and Answers'' issued on July, 23, 2024 (89 FR 
59740). FDA considered comments received on the draft guidance as the 
guidance was finalized. Changes from the draft to the final guidance 
include: (1) further aligning recommendations in the guidance with the 
principles in ICH Q5E; (2) clarifying recommendations for leveraging 
comparative analytical assessment data from an original 351(k) 
biologics license application (351(k) BLA); and (3) clarifying edits to 
Q&A 4 on the nature and type of information that FDA recommends to 
support approval of a supplement for a dosage form or a strength that 
has not previously been licensed under the 351(k) BLA. Additional 
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 ``Postapproval Manufacturing Changes to 
Biosimilar and Interchangeable Biosimilar Products: Questions and 
Answers.'' 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.
    FDA considered the applicability of Executive Order 14192, per OMB 
guidance in M-25-20, and finds this action to be neither an E.O. 14192 
regulatory action nor an E.O. 14192 deregulatory action.

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 201.56 and 201.57 relating to the content and format 
requirements for labeling of drug and biological products have have 
been approved under OMB control number 0910-0572. The collections of 
information in 21 CFR parts 210 and 211 relating to current good 
manufacturing practice requirements have been approved under OMB 
control

[[Page 64933]]

number 0910-0139. The collections of information in section 351(k) of 
the PHS Act relating to biosimilar and interchangeable biosimilar 
product applications have been approved under OMB control number 0910-
0718. The collections of information in section 351(a) of the PHS Act 
and 21 CFR part 601 relating to biologics license applications (BLA) 
have been approved under OMB control number 0910-0338.

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/biologics-guidances">https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances</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>.

Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-20817 Filed 10-9-26; 8:45 am]
BILLING CODE 4164-01-P


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