[Federal Register Volume 88, Number 179 (Monday, September 18, 2023)]
[Notices]
[Pages 63957-63960]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-20141]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-0643]


Labeling for Biosimilar and Interchangeable Biosimilar Products; 
Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``Labeling 
for Biosimilar and Interchangeable Biosimilar Products.'' This draft 
guidance is intended to help applicants develop draft labeling for 
proposed

[[Page 63958]]

biosimilar and interchangeable biosimilar products. The recommendations 
for biosimilar and interchangeable biosimilar product labeling in this 
draft guidance pertain only to the prescribing information, except for 
certain recommendations pertaining to FDA-approved patient labeling 
(e.g., Patient Information, Medication Guide, Instructions for Use). 
This draft guidance provides an overview of FDA's recommendations for 
labeling for biosimilar and interchangeable biosimilar products. When 
finalized, this draft guidance will revise and replace the guidance for 
industry entitled ``Labeling for Biosimilar Products.''

DATES: Submit either electronic or written comments on the draft 
guidance by November 17, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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-2016-D-0643 for ``Labeling for Biosimilar and Interchangeable 
Biosimilar Products.'' 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 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: Sandra Benton, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 1132, Silver Spring, MD 20993, 301-796-
1042, [email protected]; or Anne Taylor, 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 ``Labeling for Biosimilar and Interchangeable Biosimilar 
Products.'' Section 351(k) of the Public Health Service Act (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. Section 351(k) of the PHS Act sets 
forth the requirements for an application for a proposed biosimilar 
product and an application or a supplement for a proposed 
interchangeable biosimilar product. Under section 351(k) of the PHS 
Act, a proposed biological product that is demonstrated to be 
biosimilar to, or interchangeable with, a reference product can rely on 
certain existing scientific knowledge about the safety, purity, and 
potency of the reference product to support licensure, and this is 
reflected in the approach to biosimilar and interchangeable biosimilar 
product labeling.
    In this draft guidance, FDA outlines its recommendations for 
biosimilar and interchangeable biosimilar product labeling. A 
demonstration of biosimilarity or interchangeability means, among other 
things, that FDA has determined that there are no clinically meaningful 
differences between the proposed product and the

[[Page 63959]]

reference product in terms of safety, purity, and potency. Accordingly, 
the draft guidance includes a recommendation that biosimilar and 
interchangeable biosimilar product applicants should incorporate 
relevant data and information from the reference product labeling, with 
appropriate modifications.
    When finalized, this draft guidance will revise and replace the 
guidance for industry entitled ``Labeling for Biosimilar Products'' 
(available at https://www.fda.gov/media/96894/download) issued July 19, 
2018 (83 FR 34141). Significant changes from the final to this draft 
include recommendations on the following topics:
     Labeling for interchangeable biosimilar products;
     Product identification when the reference product labeling 
describes a clinical study conducted with a non-U.S.-approved 
biological product;
     Pediatric use statements; and
     Incorporating relevant immunogenicity data and information 
from the reference product labeling in the biosimilar or 
interchangeable biosimilar product labeling.
    This draft guidance also addresses topics previously addressed in 
Q.I.27 and Q.I.28 of the draft guidance ``Biosimilarity and 
Interchangeability: Additional Draft Q&As on Biosimilar Development and 
the BPCI Act'' issued on November 19, 2020 (Additional Draft Q&As 
guidance). FDA considered comments it received regarding these Q&As 
when preparing this draft guidance. The Additional Draft Q&As guidance 
has been revised to remove Q.I.27 and Q.I.28, with the remaining Q&As 
unchanged. The remaining Q&As can be found in the draft guidance 
``Biosimilarity and Interchangeability: Additional Draft Q&As on 
Biosimilar Development and the BPCI Act (Revision 1).''
    Eight years have passed since FDA approved the first biosimilar 
product. In this time, FDA has approved over 40 biosimilar products, 
including multiple interchangeable biosimilar products, and has gained 
valuable experience about labeling considerations for biosimilar and 
interchangeable biosimilar products, including labeling statements in 
the Highlights of the Prescribing Information that explain 
biosimilarity and interchangeability. First, it has become clear that 
an applicant may choose to submit a single 351(k) biologics license 
application (BLA) seeking to license both biosimilar and 
interchangeable biosimilar products. Draft labeling for such 
applications would need to address both biosimilar and interchangeable 
biosimilar products, and the status of a particular product within such 
a BLA can change over time, for example, as relevant exclusivities 
expire. Determining how to appropriately label such products and keep 
labeling up to date without causing undue confusion has proven 
challenging. Moreover, a labeling statement noting that certain 
products within a 351(k) BLA have been approved as interchangeable, and 
explaining the interchangeability standard, is not likely to be useful 
to prescribers, who can prescribe both biosimilar and interchangeable 
biosimilar products in place of the reference product with equal 
confidence that they are as safe and effective as their reference 
products. Additionally, FDA's Purple Book Database of Licensed 
Biological Products (the Purple Book) (available at https://purplebooksearch.fda.gov) has evolved as a resource for patients, 
pharmacists, physicians, and other health care providers to easily 
identify approved biosimilar and interchangeable biosimilar products. 
Because the Purple Book is available as an easy-to-use resource for 
pharmacists, and interchangeability, as defined in section 351(i)(3) of 
the PHS Act, pertains to substitution of an interchangeable biosimilar 
product for its reference product ``without the intervention of the 
[prescribing] health care provider'' (i.e., pharmacy-level 
substitution), information about interchangeability is more 
appropriately located in the Purple Book rather than labeling. 
Consistent with this evolution in our thinking, the draft guidance 
states that both biosimilar and interchangeable biosimilar products 
should contain the same biosimilarity statement in the Highlights of 
the Prescribing Information. This statement is applicable to biosimilar 
and interchangeable biosimilar products. Accordingly, as described 
above, FDA has withdrawn the Q&As in its Additional Draft Q&As guidance 
regarding inclusion of an interchangeability statement in the labeling 
of products licensed as interchangeable.
    Finally, we invite comment on biosimilarity statements, such as a 
statement described in section IV.C.1.b of the draft guidance, in the 
Highlights of the Prescribing Information. Specifically, FDA invites 
comment on how useful such biosimilarity statements have been for 
healthcare practitioners and the public, whether such statements can be 
improved to provide more clarity on what biosimilarity means, and 
whether biosimilar and interchangeable biosimilar product labeling 
should include such a statement at all.
    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 ``Labeling for 
Biosimilar and Interchangeable Biosimilar Products.'' 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. Therefore, 
clearance by the Office of Management and Budget (OMB) under the 
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not 
required for this guidance. The previously approved collections of 
information are subject to review by OMB under the PRA. The collections 
of information for the submission of a BLA under section 351(k) of the 
PHS Act have been approved under OMB control number 0910-0718; the 
collections of information in 21 CFR 201.56 and 201.57 for the 
submission of labeling have been approved under OMB control number 
0910-0572; the collections of information in 21 CFR part 208 for 
Medication Guides have been approved under OMB control number 0910-
0393; the collections of information in 21 CFR 312.47 for meetings with 
FDA have been approved under OMB control number 0910-0014; the 
collections of information in 21 CFR part 600 for the submission of 
adverse experience reporting for licensed biological products and 
general records have been approved under OMB control number 0910-0308; 
and the collections of information in 21 CFR part 601 for the 
submission of labeling in a BLA or supplement to a BLA 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-information-biologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.


[[Page 63960]]


    Dated: September 13, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-20141 Filed 9-15-23; 8:45 am]
BILLING CODE 4164-01-P