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Regulatory Focus™ > News Articles > FDA Releases Long-Awaited Draft Guidance on Biosimilar Labeling

FDA Releases Long-Awaited Draft Guidance on Biosimilar Labeling

Posted 31 March 2016 | By Zachary Brennan 

FDA Releases Long-Awaited Draft Guidance on Biosimilar Labeling

The US Food and Drug Administration (FDA) on Thursday unveiled draft guidance on biosimilar labels, which will rely heavily on their reference products’ labels, though the biologics industry will likely be happy that the labels must make certain clarifications about the biosimilar and reference product.

At the outset of the 15-page guidance, FDA makes clear that biosimilar product labeling should not include a description of a clinical study that merely supports a demonstration that there are no clinically meaningful differences between the proposed biosimilar and the reference product for the approved indications.

“Data from clinical studies designed to support a demonstration of biosimilarity are not likely to be relevant to a health care practitioner’s considerations regarding safe and effective use of the biosimilar product and potentially may cause confusion, resulting in an inaccurate understanding of the risk-benefit profile of the product,” FDA says. “For example, the endpoints used in a clinical study intended to support a demonstration of no clinically meaningful differences may not be the same endpoints studied to support approval of the reference product and may not inform prescribing decisions regarding safety and efficacy.”

Duncan Emerton, senior director at FirstWord Pharma, told Focus that the guidance doesn’t have any major surprises as it aligns with the way FDA labelled the first approved biosimilar in the US, Zarxio (filgrastim-sndz), “ie. like a generic.” However, Emerton says he’s spoken to lots of physicians “and the general consensus has been a need for full disclosure (i.e. include all the relevant data for the biosimilar whenever possible).”

Data on Label

FDA says that like with generics, biosimilar labeling should include a description of the clinical data that supported safety and efficacy of the reference product. AbbVie argued in a citizen petition with FDA last year that biosimilars should not be labeled like generic drugs.

But in circumstances where a biosimilar is not approved for the same indications as its reference product, unlike with generic drugs, FDA notes that “it may be necessary to include information in the biosimilar product labeling relating to an indication(s) for which the biosimilar product applicant is not seeking licensure, in order to help ensure safe use (e.g., when safety information in the reference product labeling is related to use of the product and is not specific to a particular approved indication(s) or when information specific to only the biosimilar product’s indication(s) cannot be easily extracted).”

And the label should be written in a manner that does not imply that the biosimilar product is approved for a reference product indication(s) or use(s) that has not been approved for the biosimilar product, the draft guidance says.

“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 product labeling may not have been reported with the biosimilar product at the time of licensure,” FDA adds.

Leah Christl, Ph.D., Associate Director for Therapeutic Biologics and lead of the Therapeutic Biologics and Biosimilars Staff in the Office of New Drugs, said: “The biosimilar labeling guidance has been issued in draft to provide an opportunity for public comment and we hope to hear from the various stakeholder communities - industry, health care providers, and patients. We will review and consider all of the comments received as we work to finalize guidance on this topic.”

Biosimilar-Specific Info

In addition, biosimilar product labeling may include information specific to the biosimilar 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, FDA says.

“In cases where the biosimilar product applicant is not seeking approval for all the indications for which the reference product is licensed, the combined data described in the reference product labeling should be included in the biosimilar product labeling in a manner that is not indication-specific. However, any text that refers to an indication for which licensure has not been sought by the biosimilar product applicant and is included to ensure safe use of the biosimilar product should be revised to avoid an implication that the biosimilar has been approved for that indication(s),” FDA says.

But in sections of the biosimilar product labeling that are based on the reference product, FDA anticipates that the text will be similar, though the label does not necessarily have to be identical to the reference product.

Sample Text

FDA also offers illustrative examples with a fictional reference product JUNEXANT (replicamab-hjxf) and a fictional biosimilar product NEXSYMEO (replicamab-cznm).

In labeling sections where the risk applies to both the biosimilar product and the reference product (e.g., BOXED WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS (Postmarketing Experience)), it would be appropriate to use the core name of the reference product followed by the word “products” (i.e., replicamab products) to convey, for example, that a risk or other information necessary for the safe use of the product applies to both the biosimilar and the reference product.

In sections where the information described is specific to the biosimilar product — i.e. INDICATIONS AND USAGE, DOSAGE AND ADMINISTRATION, DOSAGE FORMS AND STRENGTHS, DESCRIPTION, and HOW SUPPLIED/STORAGE AND HANDLING – FDA says:

  • 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 BOXED WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and DRUG INTERACTIONS sections.
  • When clinical studies or data derived from studies with the reference product are described in the biosimilar labeling, the reference product’s proper name should be used. This information would typically be included in sections such as, but not limited to, ADVERSE REACTIONS (Clinical Trials Experience) and CLINICAL STUDIES.


For sections such as “WARNINGS AND PRECAUTIONS” and “ADVERSE REACTIONS,” the reference product labeling may group the events by type from all the reference product clinical trials for all the indications for which the reference product is licensed.

What the label should include in the “Highlights” section:

  • Initial US approval date;
  • Biosimilarity statement (on the line immediately beneath the initial approval date in Highlights, that the product is biosimilar to the reference product. It 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 appear as a footnote symbol inserted after the word “biosimilar.” The end of the statement should include a cross-reference to the INDICATIONS AND USAGE section.

For example, FDA says, for the fictitious product NEXSYMEO, the statement should read: NEXSYMEO (replicamab-cznm) is biosimilar* to JUNEXANT (replicamab-hjxf) for the indications listed. (1) The footnote should appear at the end of Highlights (but above the Revision Date) and 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.

Information in “INDICATIONS AND USAGE” should be specific to the approved indications for the biosimilar product and should be consistent with language previously approved for the reference product for those indications, the guidance says. The biosimilar product labeling also should include text from the reference product labeling regarding any “Limitations of Use” relevant to the biosimilar’s indication(s).

FDA adds that immunogenicity information is usually placed in a subsection in the ADVERSE REACTIONS section entitled Immunogenicity. And to help health care practitioners interpret the significance of the information, the following (or a similar) statement should be included as the first paragraph in the subsection, FDA says, noting that it should precede the immunogenicity data based on the reference 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 to [reference product’s proper name] in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.”

Labeling for Biosimilar Products Guidance for Industry

From our perspective: Biosimilar product labeling



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