4164-01-P
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2017-D-0154]
Considerations in Demonstrating Interchangeability With a Reference Product: Update;
Draft Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is announcing the
availability of a draft guidance for industry entitled “Considerations in Demonstrating
Interchangeability With a Reference Product: Update.” This draft guidance describes
considerations regarding a switching study or studies intended to support a demonstration that a
proposed therapeutic protein product is interchangeable with a reference product for the purposes
of submitting a marketing application or supplement under the Public Health Service Act (PHS
Act). After considering any comments received in the docket for this draft guidance, we intend
to revise the final guidance for industry entitled “Considerations in Demonstrating
Interchangeability With a Reference Product” issued on May 14, 2019, to amend sections in that
document regarding the subject addressed in this draft guidance.
DATES: Submit either electronic or written comments on the draft guidance by [INSERT
DATE 60 DAYS AFTER DATE OF PUBLICATION IN THE FEDERAL REGISTER] 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that the Agency considers your comment on this draft guidance before it begins work on the final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:

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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.

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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-2017-D-0154

for “Considerations in Demonstrating Interchangeability With a Reference Product: Update.”
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.

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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 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; 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 draft 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; or James Myers, 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 draft guidance for industry entitled
“Considerations in Demonstrating Interchangeability With a Reference Product: Update.” This
draft guidance describes considerations regarding a switching study or studies intended to
support a demonstration that a proposed therapeutic protein product is interchangeable with a
reference product for the purposes of submitting a marketing application or supplement under
section 351(k) of the PHS Act (42 U.S.C. 262(k)). After considering any comments received in
the docket for this draft guidance, we intend to revise the final guidance for industry entitled
“Considerations in Demonstrating Interchangeability With a Reference Product”
(Interchangeability Guidance) issued on May 14, 2019 (84 FR 21342) to amend sections in that
document regarding the subject addressed in this draft guidance.
FDA issued the Interchangeability Guidance before receiving and reviewing any
biologics license applications submitted under section 351(k) of the PHS Act for a proposed
interchangeable biosimilar product. Since publication of the Interchangeability Guidance,
experience has shown that for the products approved as biosimilars to date, the risk in terms of
safety or diminished efficacy is insignificant following single or multiple switches between a

reference product and a biosimilar product. Accordingly, FDA’s scientific approach to when a
switching study or studies may be needed to support a demonstration of interchangeability has
evolved.
This draft guidance is not intended to be finalized as a standalone guidance. Instead, the
recommendations in this draft guidance, when finalized, are intended to revise the
Interchangeability Guidance and to replace sections in that document, such as sections VI.A and
VII, to reflect FDA’s current thinking regarding the subject addressed in this guidance. FDA is
issuing this draft guidance to seek public comment through the accompanying docket.
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.
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 for the
submission of a biologics license application or supplemental application under section 351(k) of
the PHS Act have been approved under OMB control number 0910-0718. The collections of
information in 21 CFR part 312 for the submissions of investigational new drug applications
have been approved under OMB control number 0910-0014. The collections of information in
21 CFR part 314 for the submissions of new drug applications have been approved under OMB
control number 0910-0001. The collections of information in 21 CFR part 601 for the
submissions of biologics license application and supplemental applications have been approved
under OMB control number 0910-0338.
III. Electronic Access

Persons with access to the internet may obtain the draft guidance at
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs,
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-informationbiologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidancedocuments, or https://www.regulations.gov.
Dated: June 13, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-13429 Filed: 6/20/2024 8:45 am; Publication Date: 6/21/2024]