Labeling for Biosimilar
Products
Guidance for Industry

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)

July 2018
Labeling

Labeling for Biosimilar
Products
Guidance for Industry
Additional copies are available from:
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Center for Drug Evaluation and Research
Food and Drug Administration
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Email: ocod@fda.hhs.gov
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
July 2018
Labeling

Contains Nonbinding Recommendations
TABLE OF CONTENTSI.

INTRODUCTION............................................................................................................. 1II.

BACKGROUND ............................................................................................................... 1

III.
GENERAL PRINCIPLES FOR DRAFT LABELING OF PROPOSEDBIOSIMILAR PRODUCTS (BIOSIMILAR PRODUCT LABELING) ................................. 3
IV.
SPECIFIC RECOMMENDATIONS ON CONTENT OF BIOSIMILAR PRODUCTLABELING ................................................................................................................................... 5A.

Approaches to Product Identification .......................................................................................... 5

B.

Approaches to Content Presentation............................................................................................ 7

C.

Approaches to Specific Sections of Biosimilar Product Labeling .............................................. 8V.

FDA-APPROVED PATIENT LABELING .................................................................. 10

VI.

REVISING BIOSIMILAR PRODUCT LABELING .................................................. 10A.

Updating Safety Information ...................................................................................................... 10

B.

Additional Conditions of Use ...................................................................................................... 11VII.

HOW TO SUBMIT INITIAL AND REVISED LABELING ..................................... 11

VIII. INTERCHANGEABLE PRODUCTS .......................................................................... 12

Contains Nonbinding Recommendations

Labeling for Biosimilar Products
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. 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.
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on thetitle page.

I.

INTRODUCTION

This guidance is intended to help applicants develop draft labeling for proposed biosimilar
products for submission in an application under section 351(k) of the Public Health Service Act(PHS Act) (42 U.S.C. 262(k)). The recommendations for prescription drug labeling in thisguidance pertain only to the prescribing information (commonly referred to as the package
insert), except for certain recommendations in section V pertaining to FDA-approved patientlabeling (e.g., Patient Information, Medication Guide, and Instructions for Use).2 This guidance
does not provide specific labeling recommendations for interchangeable products (seesection VIII of this guidance).
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.

II.

BACKGROUND

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was enacted as part of
the Patient Protection and Affordable Care Act (Affordable Care Act) (Public Law 111-148) on
March 23, 2010. The BPCI Act amends the PHS Act and other statutes to create an abbreviatedlicensure pathway for biological products shown to be biosimilar to or interchangeable with an
1

This guidance has been prepared by the Office of New Drugs, Therapeutic Biologics and Biosimilars Staff, in theCenter for Drug Evaluation and Research (CDER) in cooperation with the Center for Biologics Evaluation andResearch (CBER) at the Food and Drug Administration.
2

Unless otherwise specified, the terms biosimilar product labeling and labeling as used in this guidance address
only the prescribing information as described in 21 CFR 201.56 and 201.57.

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FDA-licensed reference product3 (see sections 7001 through 7003 of the Affordable Care Act).
Section 351(k) of the PHS Act, added by the BPCI Act, sets forth the requirements for an
application for a proposed biosimilar product and an application or a supplement for a proposedinterchangeable product.
Section 351(i) of the PHS Act defines biosimilarity to mean “that the biological product is highly
similar to the reference product notwithstanding minor differences in clinically inactive
components” and that “there are no clinically meaningful differences between the biologicalproduct and the reference product in terms of the safety, purity, and potency of the product.”
To meet the standard for interchangeability, an applicant must provide sufficient information todemonstrate biosimilarity and also to demonstrate that the biological product can be expected to
produce the same clinical result as the reference product in any given patient and, if thebiological product is administered more than once to an individual, the risk in terms of safety or
diminished efficacy of alternating or switching between the use of the biological product and thereference product is not greater than the risk of using the reference product without suchalternation or switch (see section 351(k)(4) of the PHS Act). Interchangeable products may besubstituted for the reference product without the intervention of the prescribing health careprovider (see section 351(i)(3) of the PHS Act).
An application submitted under section 351(k) of the PHS Act must contain, among other things,
information demonstrating that the biological product is biosimilar to a reference product based
upon data derived from:•

Analytical studies that demonstrate that the biological product is highly similar to thereference product notwithstanding minor differences in clinically inactive components;•

Animal studies (including the assessment of toxicity); and•A clinical study or studies (including the assessment of immunogenicity andpharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity,and potency in one or more appropriate conditions of use for which the reference productis licensed and intended to be used and for which licensure is sought for the biologicalproduct.

Under the PHS Act, FDA has the discretion to determine that an element described above is
unnecessary in a 351(k) application.
Under FDA regulations, prescription drug labeling must provide adequate information to enable
health care providers to “use the drug safely and for the purposes for which it is intended”; and to
this end, the approved prescribing information summarizes the essential scientific information
3

Reference product means the single biological product licensed under section 351(a) of the PHS Act against whicha biological product is evaluated in a 351(k) application (section 351(i)(4) of the PHS Act).

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needed by health care providers for the safe and effective use of a drug.4 Prescription druglabeling reflects FDA’s finding of safety and effectiveness5,6 for the drug under the labeledconditions of use and facilitates prescribing decisions, thereby enabling the safe and effective useof drugs, including biological products, and reducing the likelihood of medication errors.

III.

GENERAL PRINCIPLES FOR DRAFT LABELING OF PROPOSEDBIOSIMILAR PRODUCTS (BIOSIMILAR PRODUCT LABELING)

The goal of a biosimilar product development program is to demonstrate biosimilarity between
the proposed product and the reference product — not to independently establish safety andeffectiveness of the proposed product. A demonstration of biosimilarity means, among otherthings, that FDA has determined that there are no clinically meaningful differences between the
proposed product and the reference product in terms of safety, purity, and potency.7 Thus,
FDA’s finding of safety and effectiveness for the reference product, as reflected in its FDAapproved prescribing information, may be relied upon to provide health care providers with theessential scientific information needed to facilitate prescribing decisions for the proposedbiosimilar product’s labeled conditions of use (e.g., indication(s), dosing regimen(s)).
Accordingly, FDA recommends that biosimilar product labeling incorporate relevant data andinformation from the reference product labeling, with appropriate modifications, such as thosedescribed in sections V and VI of this guidance.8
Information and data from a clinical study of a proposed biosimilar product should be describedin its labeling only when necessary to inform safe and effective use by a health care provider. As
a general matter, it is FDA’s view that biosimilar product labeling should not include a
description of or data from clinical studies conducted to support a demonstration ofbiosimilarity.9 Generally, clinical studies conducted to support a demonstration of biosimilarity
4

See 21 CFR 201.100 and 201.56(a)(1).

5

The standard for licensure of a biological product as potent under section 351(a) of the PHS Act has long beeninterpreted to include effectiveness (see 21 CFR 600.3(s) and the guidance for industry Providing Clinical Evidenceof Effectiveness for Human Drug and Biological Products). We update guidances periodically. For the most recent
version of a guidance, check the FDA guidance web page athttps://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
6

In this guidance, we use the terms safety and effectiveness and safety, purity, and potency interchangeably in thediscussions pertaining to biosimilar products.
7

Section 351(i)(2) of the PHS Act.

8

Sections V and VI of this guidance describe examples of areas in which the reference product labeling andbiosimilar product labeling might differ.
9

FDA posts on its website certain documents generated by FDA related to its review of a 351(k) application, as
appropriate. For products regulated by CDER, see Drugs@FDA(https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm). For products regulated by CBER, see the CBER
Freedom of Information Office Electronic Reading Room

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are not designed to support an independent demonstration of safety or effectiveness of the
proposed biosimilar product and thus would generally not be expected to facilitate anunderstanding of product safety and effectiveness. For example, the endpoints used in a clinicalstudy conducted to support a demonstration of no clinically meaningful differences may not be
the same endpoints evaluated to support licensure of the reference product and thus may not
inform prescribing decisions regarding safety and effectiveness. Similarly, the patient
population may differ from the patient population studied in the clinical trials that supported thedetermination of safety and effectiveness of the reference product. For example, subjects in astudy conducted to support a demonstration of no clinically meaningful differences between thebiosimilar product and the reference product may be healthy volunteers, or the condition of use
studied may be one for which the reference product is not licensed or for which the applicant of
the biosimilar product is not seeking licensure but for which sufficient data indicate that the
population or condition of use is adequately sensitive to detect clinically meaningful differences
between the products, should they exist.
Because clinical studies conducted to support a demonstration of biosimilarity generally are notdesigned to support an independent demonstration of safety or effectiveness, such studies may be
misinterpreted in the context of drug labeling, resulting in an inaccurate understanding of therisk-benefit profile of the biosimilar product. Therefore, studies conducted to support
biosimilarity generally should not be included in biosimilar product labeling. Biosimilar productlabeling should incorporate relevant data and information from the reference product labeling,including clinical data that supported FDA’s finding of safety and effectiveness of the reference
product.
As required under 21 CFR 201.56(c)(1), biosimilar product labeling must meet the content andformat requirements of the physician labeling rule (PLR) as described in 21 CFR 201.56(d) and
201.57, regardless of the format of the reference product labeling.10 In addition, biosimilar
product labeling must meet the content and format requirements of the pregnancy and lactation
labeling final rule (PLLR) as described in 21 CFR 201.57(c)(9)(i) through (iii), regardless ofwhether the reference product must meet these requirements.11(https://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm129132.htm).
Health care providers and others can refer to those documents if interested in FDA’s review of data and information
submitted in a 351(k) application to support biosimilarity.
See the final rule “Requirements on Content and Format of Labeling for Human Prescription Drug and Biological
Products” (71 FR 3922, January 24, 2006). This rule is commonly referred to as the physician labeling rule because
it addresses prescription drug labeling that is used by prescribing physicians and other health care providers. Also
see additional labeling guidances athttps://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm084159.htm.
10

See the final rule “Content and Format of Labeling for Human Prescription Drug and Biological Products;
Requirements for Pregnancy and Lactation Labeling” (79 FR 72064, December 4, 2014). The final rule describes
the implementation schedule for applications submitted on or after the effective date of the rule, applications
pending at the time the rule became effective, and applications approved before the rule became effective (79 FR
72064 at 72095–96).
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IV.

SPECIFIC RECOMMENDATIONS ON CONTENT OF BIOSIMILAR PRODUCTLABELING

FDA recommends that biosimilar product labeling incorporate relevant data and informationfrom the reference product labeling, with appropriate modifications, as explained in sections V
and VI of this guidance. The relevant data and information from the reference product labelingthat should be incorporated into the biosimilar product labeling will depend on whether theapplicant is seeking licensure for all conditions of use (e.g., indication(s), dosing regimen(s)) or
fewer than all conditions of use of the reference product for the biosimilar product.12
In sections of the biosimilar product labeling that are based on the reference product labeling, it
is anticipated that the text will be similar to the corresponding text in the reference productlabeling. Text based on the reference product labeling need not be identical to the reference
product labeling and should reflect currently available information necessary for the safe andeffective use of the biosimilar product. Certain differences between the biosimilar and reference
product labeling may be appropriate. For example, biosimilar product labeling conforming to
PLR and/or PLLR may differ from reference product labeling because the reference productlabeling may not be required to conform to those requirements at the time of licensure of thebiosimilar product. In addition, biosimilar product labeling may include information specific tothe biosimilar product that is necessary to inform safe and effective use of the product, including
administration, preparation, storage, or safety information. This information may differ from thatof the reference product labeling when it reflects differences between the biosimilar product andthe reference product that do not preclude licensure of the biosimilar product.
A.

Approaches to Product Identification

In biosimilar product labeling, the approach to product identification depends on the context of
the information being presented. FDA acknowledges that there will be variations on the general
concepts outlined in this section because the approach to product identification will depend on
the specific statements. The illustrative examples in this section use a fictional reference product
JUNEXANT (replicamab-hjxf) and a fictional biosimilar product NEXSYMEO (replicamabcznm).

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A biosimilar product applicant generally may seek licensure for fewer than all conditions of use for which thereference product is licensed. The 351(k) application must include information demonstrating that the condition orconditions of use prescribed, recommended, or suggested in the proposed labeling submitted for the proposedbiosimilar product have been previously licensed for the reference product (see section 351(k)(2)(A)(i)(III) of the
PHS Act).

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1. When use of the biosimilar product name is recommended:
The biosimilar product name should be used in labeling text that is specific to the biosimilar
product or that refers solely to the biosimilar product. If a biosimilar product has a proprietary
name, the proprietary name (e.g., NEXSYMEO) should be used in the appropriate sections.
However, if a proprietary name is not available, or if referring to the drug substance (asdiscussed below), the biosimilar product’s proper name (e.g., replicamab-cznm) should be
used.13
The biosimilar product’s proprietary name (or, if a proprietary name is not available, thebiosimilar product’s proper name) should be used in circumstances such as the following:In sections where the information described is specific to the biosimilar product — This
includes, but is not limited to, the following sections: INDICATIONS AND USAGE,DOSAGE AND ADMINISTRATION, DESCRIPTION, and HOW
SUPPLIED/STORAGE AND HANDLING.



For directive statements and recommendations for preventing, monitoring, managing, or
mitigating risks (e.g., “Discontinue NEXSYMEO in patients with [adverse reaction]”) —Such statements are typically included in, but are not limited to, the BOXEDWARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, andDRUG INTERACTIONS sections.

The biosimilar product’s proper name should be used when referring to the drug substance. An
example would be to use the biosimilar product’s proper name in the DESCRIPTION section.
2. When use of the reference product name is recommended:
When clinical studies or data derived from studies with the reference product are described inbiosimilar product labeling, the reference product’s proper name (e.g., replicamab-hjxf) should
be used. This information would typically be included in sections such as, but not limited to,
ADVERSE REACTIONS (Clinical Trials Experience subsection) and CLINICAL STUDIES.
3. When use of the core name is recommended:14
The overall risk-benefit profile of the reference product is relevant to the biosimilar product,even if a particular serious adverse reaction or other risk included in the reference productlabeling may not have been reported with the biosimilar product at the time of licensure. In
labeling sections where the risk applies to both the biosimilar product and the reference product13

The proper name is the nonproprietary name designated by FDA in the license for a biological product licensed
under the PHS Act (see section 351(a)(1)(B)(i) of the PHS Act and 21 CFR 600.3(k)).
14

Two examples of a core name are filgrastim and epoetin alfa. The proper name for biological products will
include a distinguishing suffix composed of four lowercase letters attached to the core name with a hyphen.

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Contains Nonbinding Recommendations(e.g., BOXED WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS,ADVERSE REACTIONS (Postmarketing Experience subsection)), it would be appropriate touse the core name of the reference product followed by the word “products” (e.g., replicamab
products) to convey, for instance, that a risk or other information necessary for the safe use of
the product applies to both the biosimilar product and the reference product (see section IV.B ofthis guidance).
For example, in WARNINGS AND PRECAUTIONS:
Reference Product Labeling
Treatment with JUNEXANT increases
the risk of serious infections involving
various organ systems and sites that may
lead to hospitalization or death.

Biosimilar Product Labeling
Treatment with replicamab products
increases the risk of serious infections
involving various organ systems and sitesthat may lead to hospitalization or death.

4. When use of more than one product name is recommended:
There may be text appropriately based on the reference product labeling where more than one ofthese product identification approaches should be used to convey information accurately.
Therefore, all text in biosimilar product labeling, even sections that have been based on reference
product labeling, should be carefully evaluated for the most appropriate product identification
approach. In some cases, such as the following example, more than two of the approaches may
be used:Replicamab products can cause hepatoxicity and acute hepatic failure. In clinical trials of
replicamab-hjxf, 10% of patients developed elevated ALT or AST greater than threetimes the upper limit of normal and 5% progressed to acute hepatic failure. Evaluate
serum transaminases (ALT and AST) and bilirubin at baseline and monthly during
treatment with NEXSYMEO . . .
B.

Approaches to Content Presentation

The labeling for the biosimilar product should be specific to the conditions of use (e.g.,indication(s), dosing regimen(s)) sought for the biosimilar product and should be consistent withlanguage previously approved for the reference product for those conditions of use.
When a biosimilar product applicant obtains licensure for fewer than all conditions of use (e.g.,indication(s), dosing regimen(s)) for which the reference product is licensed, certain text in thereference product labeling related to condition(s) of use for the reference product that are notlicensed for the biosimilar product would generally not be included in the biosimilar productlabeling.15 However, in certain circumstances it may be necessary to include information in thebiosimilar product labeling relating to an indication(s) for which the biosimilar product is not
15

See Q.I.7 in the guidance for industry Biosimilars: Questions and Answers Regarding Implementation of the
Biologics Price Competition and Innovation Act of 2009.

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licensed, in order to help ensure safe use (e.g., when safety information in the reference productlabeling is related to use of the product and is not specific to a particular licensed indication(s) or
when information specific to only the biosimilar product’s indication(s) cannot be easily
extracted).16 Such text should be written in a manner that does not imply that the biosimilar
product is licensed for a reference product indication(s) or use(s) that has not been licensed forthe biosimilar product. In these circumstances, specific sections of labeling that could be
affected include BOXED WARNING, CONTRAINDICATIONS, WARNINGS AND
PRECAUTIONS, ADVERSE REACTIONS, DRUG INTERACTIONS, and USE IN SPECIFICPOPULATIONS.
For example, for sections such as WARNINGS AND PRECAUTIONS and ADVERSE
REACTIONS, the reference product labeling may pool and categorize events from all thereference product clinical trials for all the indications for which the reference product is licensed.
In cases where the biosimilar product applicant is not seeking licensure for all the indications forwhich the reference product is licensed, the pooled data described in the reference productlabeling should be included in the biosimilar product labeling in a manner that is not indicationspecific. However, any text that refers to an indication for which the biosimilar productapplicant is not currently seeking licensure and is included to ensure safe use of the biosimilar
product should be revised to avoid an implication that the biosimilar has been licensed for thatindication(s).
C.

Approaches to Specific Sections of Biosimilar Product Labeling

1.

HIGHLIGHTS OF PRESCRIBING INFORMATION (Highlights)a.

Initial U.S. approval

The initial U.S. approval in the Highlights section is the year that the biosimilar product islicensed.
b.

Biosimilarity statement

FDA recommends including a statement, placed on the line immediately beneath the initial U.S.
approval in the Highlights section, that the product is biosimilar to the reference product. It
should read as follows:[BIOSIMILAR PRODUCT’S PROPRIETARY NAME (biosimilar product’s propername)] is biosimilar* to [REFERENCE PRODUCT’S PROPRIETARY NAME
(reference product’s proper name)].
The asterisk should appear as a footnote symbol inserted after the word “biosimilar.”16

See also 21 CFR 201.57(c)(6)(i).

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For example, for the fictitious product NEXSYMEO, the statement should read as follows:
NEXSYMEO (replicamab-cznm) is biosimilar* to JUNEXANT (replicamab-hjxf).
The footnote should appear at the end of the Highlights section (but above the Revision Date)and state the following:*Biosimilar means that the biological product is approved based on data demonstratingthat it is highly similar to an FDA-approved biological product, known as a reference
product, and that there are no clinically meaningful differences between the biosimilar
product and the reference product. Biosimilarity of [BIOSIMILAR PRODUCT’SPROPRIETARY NAME] has been demonstrated for the condition(s) of use (e.g.,indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) ofadministration described in its Full Prescribing Information.
2.

INDICATIONS AND USAGE

Information in the INDICATIONS AND USAGE section should be specific to the licensed
indications for the biosimilar product and should be consistent with information previously
approved for the reference product. The biosimilar product labeling should include text from thereference product labeling regarding any Limitations of Use relevant to the biosimilar product’s
indication(s) (see section IV.B of this guidance for recommendations regarding text that refers to
an indication for which licensure has not been sought by the biosimilar product applicant).
3.

ADVERSE REACTIONS, Immunogenicity

Immunogenicity information for therapeutic protein products is usually placed in a subsection in
the ADVERSE REACTIONS section entitled Immunogenicity. To help health care providers
interpret the significance of the information, the following or a similar statement should be
included as the first paragraph in the subsection, preceding the immunogenicity data based on thereference product labeling:
As with all therapeutic proteins, there is potential for immunogenicity. The detection of
antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody)
positivity in an assay may be influenced by several factors, including assay methodology,
sample handling, timing of sample collection, concomitant medications, and underlying
disease. For these reasons, comparison of the incidence of antibodies in the studies
described below with the incidence of antibodies in other studies or to other [core name]products may be misleading.

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Contains Nonbinding RecommendationsV.

FDA-APPROVED PATIENT LABELING

If a Medication Guide is required, applicants must follow existing Medication Guide regulations
for biosimilar product labeling.17 If the FDA-approved patient labeling for the reference productincludes Patient Information, applicants should develop Patient Information for the biosimilar
product, incorporating relevant information from the Patient Information for the reference
product, with appropriate modifications.
If the FDA-approved patient labeling for the reference product includes Instructions for Use(IFU), the IFU for the proposed biosimilar product should incorporate relevant information fromthe IFU for the reference product and present the information in a similar manner. The proposed
IFU may differ from the IFU for the reference product where, for example, modified language orimages are needed to describe the biosimilar product accurately. If other changes are proposed
beyond those necessary to describe the biosimilar product accurately, applicants should discuss
proposed changes with the Agency, including whether such changes are appropriate and whether
additional data to support such changes are warranted. Additionally, if there are plans to conduct
a human factors study and the applicant intends to submit a protocol for FDA’s review, theapplicant should seek FDA input on the proposed IFU when the human factors study protocol issubmitted for FDA review. A full and final review of proposed product labeling, including the
IFU, will occur in the context of the planned 351(k) application and may be informed by any
human factors study findings submitted or other relevant data included in the application.

VI.

REVISING BIOSIMILAR PRODUCT LABELINGA.

Updating Safety Information

During the lifecycle of a biological product, changes in the labeling may be necessary to provide
updated information needed for the safe and effective use of the product. As the reference
product and biosimilar product are used more widely or under diverse conditions, newinformation may become available. This may include new risks or new information about
known risks. A biosimilar product application holder must comply with applicable requirements
regarding adverse experience review, reporting, and recordkeeping (see 21 CFR 600.80).
When new information becomes available that causes information in labeling to be inaccurate,
false, or misleading, the application holder must take steps to change the content of its productlabeling, in accordance with 21 CFR 601.12.18 All holders of marketing applications forbiological products have an ongoing obligation to ensure their labeling is accurate and up to
date.19 A biological product is misbranded, in violation of the Federal Food, Drug, and Cosmetic17

See 21 CFR part 208.

See, e.g., 21 CFR 201.56(a)(2): “In accordance with . . . [21 CFR 601.12], the labeling must be updated when
new information becomes available that causes the labeling to become inaccurate, false, or misleading.”
18

19

Ibid.

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Act (FD&C Act), when its labeling is false or misleading; does not provide adequate directions
for use and adequate warnings; or prescribes, recommends, or suggests a dosage, manner,frequency, or duration of use of the drug that is dangerous to health (see 21 U.S.C. 331(a)through (b) and 352(a), (f), and (j)).
B.

Additional Conditions of Use

FDA recognizes that a biosimilar product application holder may be interested in seeking
licensure for an additional condition(s) of use after product licensure in the following scenarios:

The biosimilar product applicant originally obtained licensure for fewer than all of theconditions of use for which the reference product is licensed and is seeking licensure forone or more of the remaining licensed conditions of use of the reference product.

The biologics license application (BLA) holder for the reference product received
licensure for a new condition of use for the reference product after the original licensureof the biosimilar product.

The biosimilar product applicant may seek licensure for an additional condition(s) of use of thereference product in these scenarios by submitting a prior approval supplement(s) to the 351(k)application that contains the necessary data and information, including draft labeling revised toinclude the additional condition(s) of use sought. For more information on how to support
licensure of the biosimilar product for an additional condition(s) of use for which the reference
product is licensed, refer to the guidance documents on biosimilar product development on
FDA’s website.20

VII.

HOW TO SUBMIT INITIAL AND REVISED LABELING

New BLAs and supplement submissions for biosimilar product labeling should include thefollowing:20



A clean version of reference product labeling that was used to develop the biosimilar
product labeling

A tracked changes and annotated version of proposed biosimilar product labelingexplaining the differences from the reference product labelingA clean version of the proposed biosimilar product labelinghttps://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm290967.htm

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VIII. INTERCHANGEABLE PRODUCTS
Any specific recommendations for labeling for interchangeable products, including any
interchangeability statement similar to the biosimilarity statement described in section IV.C.1.bof this guidance, will be provided in future guidance.

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