FDA Releases Anxiously Awaited Biosimilar Labeling Guidance, Part 2: Label Content

April 6, 2016

More on FDA’s draft guidance in our preceding FDA News article, entitled “FDA Releases Anxiously Awaited Biosimilar Labeling Guidance, Part 1: An Overview of FDA’s Recommendations.”


Late last month FDA issued a draft guidance entitled “Labeling for Biosimilar Products,” to help biosimilar product sponsors develop the draft labeling that must be submitted to the Agency.  Although the draft guidance covers a number of different topics concerning biosimilar labeling, it places an emphasis on label content.

Biosimilar product labels will rely on that of the reference product, and FDA recommends that sponsors incorporate relevant data and information from the reference products’ labeling, making appropriate product-specific modifications.  In addition, the amount of information that is incorporated from the reference product’s label into the biosimilar product’s label will depend on the condition(s) of use for which approval is sought.  For example, if the sponsor is seeking approval for all of the reference product’s conditions of use, the biosimilar product’s label will include more information from the reference product than it would if only a few of the reference product’s conditions of use were sought.

It is anticipated that the sections of the biosimilar product’s label that are based on the reference product’s labeling will be comparable to one another.  Nevertheless, the Agency states that the labels of the two products should not contain identical text, and the biosimilar product’s label “should reflect currently available information necessary for the safe and effective use” of the product.  FDA also states that certain differences between the labels of the biosimilar and reference products may be appropriate, including the following:

  • “Biosimilar product labeling conforming to PLR and/or PLLR may differ from reference product labeling because the reference product labeling may not be required to conform to those requirements at the time of licensure of the biosimilar product.”
  • “Biosimilar product labeling may include information specific to the biosimilar product necessary to inform safe and effective use of the product, which could include differences such as administration, preparation, storage, or safety information that do not otherwise preclude a demonstration of biosimilarity.”

Product Identification

In biosimilar product labeling, the context of the information being presented will impact the approach that is used to accomplish product identification.  FDA recognizes that, because the approach to product identification will depend on the specific statements that are made, the general concepts outlined in the draft guidance may vary.

Using the Biosimilar Product’s Name

The biosimilar product’s name should be used in labeling text that is specific to, or refers solely to the biosimilar product.  If the biosimilar has a proprietary name, it should be used in these instances.  If a proprietary name is unavailable, the biosimilar’s proper name, or “the nonproprietary name designated by FDA in the license for a biological product licensed under the PHS Act,” should be used.

The biosimilar’s product name should be used in the following circumstances:

  1. Where the information is specific to the biosimilar product.
  2. In directive statements and recommendations for preventing, monitoring, managing, or mitigating risks.

Using the Reference Product’s Name

The biosimilar product’s label should include the reference product’s proper name when describing clinical studies or data derived from studies with the reference product.  This information is typically found in the Adverse Reactions (Clinical Trials Experience) and Clinical Studies sections.  In addition, reference product’s proper name should also be used in the biosimilarity statement.

Using the Core Name

At the time of licensure, it is possible that some of the serious adverse reactions or other risks listed in the reference product’s label may not have been experienced with the biosimilar product.  Nonetheless, the reference product’s overall risk-benefit profile is still relevant to the biosimilar product.

In sections of the label where the risk applies to both products, the reference product’s core name, or “the component shared among related biological products as part of the proper name,” followed by the word “products” should be used.  This conveys “that a risk or other information necessary for the safe use of the product applies to both the biosimilar product and the reference product.”

Using Multiple Product Names

The label may include text “based on the reference product labeling where more than one of these product identification approaches should be used to accurately convey information.”  As such, FDA states that it is important to carefully evaluate all text included in the label to ensure that the most appropriate product identification approach has been used.

Content Presentation

Biosimilar product labeling should be specific to the conditions of use for which the sponsor is seeking approval, and should be consistent with the previously approved language for those conditions of use.

Typically, information from the reference product’s label that refers to condition(s) of use not sought by the biosimilar product’s sponsor would not need to be included on the biosimilar’s label.  However, to ensure that the product is used safely, it may be necessary for the label to include information related to an indication that is not applicable to the biosimilar product.  In order to avoid confusion among physicians and consumer, this text must be presented in a way that does not imply that the product is approved for the indication at hand.

Biosimilarity Statement

Immediately below the initial U.S. approval date, in the Highlights section of the label, sponsors should include a statement expressing that the product is biosimilar to the reference product.  FDA specifies that the statement should read as follows:

“[BIOSIMILAR PRODUCT’S PROPRIETARY NAME (biosimilar product’s proper name)] is biosimilar* to [REFERENCE PRODUCT’S PROPRIETARY NAME (reference product’s proper name)] for the indications listed. (1)”

The asterisk should be inserted as a footnote symbol following the word “biosimilar.”  The footnote should be included at the end of the Highlights section, just above the Revision Date, and should state:

“*Biosimilar means that the biological product is approved based on data demonstrating that 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.”

Additional Recommendations Regarding Label Content

The draft guidance provides a number of additional recommendations regarding the content to be included in specific sections of biosimilar product labeling, including the following sections:

  • Highlights of Prescribing Information (Highlights)
  • Indications & Usage
  • Adverse Reactions, Immunogenicity

For additional information on the content of these sections, view the FDA’s full draft guidance.

FDA is seeking public feedback on the draft guidance and is asking interested parties to submit comments by June 3, 2016.

Are you in the process of developing a biosimilar product?  Are you seeking approval of an FDA-regulated product?  We can help.  To learn more about our services and our proprietary approach to FDA, contact us today.


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