July 08, 2016

FDA's Draft Guidance to Help Manufacturers in Labeling Biosimilars

The passage of the Biologics Price Competition and Innovation Act (BPCIA) in 2010 paved the way for the introduction of biosimilars in the United States. Biosimilars are large-molecule drugs that are highly similar, but not exact duplicates of, biologic drugs such as vaccines, insulin and monoclonal antibodies used to treat serious conditions such as cancer and rheumatoid arthritis. The FDA approved the first biosimilar in the United States —Zarxio, a biosimilar of Neupogen — in March 2015. Inflectra, a biosimilar of Remecade, was then approved by the FDA in April 2016.

Until this year, little information was available to drug manufacturers as to how biosimilars should be labeled. But the FDA recently helped remove some of the uncertainty by releasing a draft guidance entitled “Labeling for Biosimilar Products: Guidance for Industry” (Draft Guidance) on March 31, 2016. Then, in a win for reference product sponsors in Amgen, Inc. v. Apotex Inc., the Federal Circuit held that the BPCIA’s 180-day notice requirement prior to commercial marketing is always mandatory for subsection k applicants.

FDA Draft Guidance

Although the Draft Guidance contains only non-binding recommendations, it provides some indication on the FDA’s current views relating to biosimilar labeling. The highlights of the Draft Guidance recommendations are as follows:

  • Overall Approach. The FDA anticipates the text in a biosimilar label be similar to the test in the reference product’s labeling. Drug manufacturers are advised to incorporate “relevant data and information from the reference product labeling, with appropriate product-specific modifications.”

  • Clinical Data. Generally speaking, information and data from a clinical study of a biosimilar product should not be included in the biosimilar product label unless necessary to inform safe and effective use by a health care practitioner.

  • “Biosimilarity Statement.” Labeling should include a statement making clear that the drug is a biosimilar, and the reference product of the biosimilar should be identified.

  • Name References. The name of the biosimilar should be referenced in portions of the labeling that specifically relate to the biosimilar, but the name of the reference product should be used when providing information relating to clinical studies or data deriving therefrom that relate only to the reference product. In portions of a label that relate both to a biosimilar and a reference product, including label sections listing contraindications, warnings and precautions, and adverse reactions, the generic name of the reference product followed by the word “products” should be used.

  • Updating Safety Information. The Draft Guidance explicitly states that the biosimilar product application holder “must promptly review all adverse drug experience information” and must “take steps to change the content of its product labeling” on an ongoing basis, and does not condition the change in content on the reference holder’s label in anyway.

Draft Guidance Product Liability Implications

The labeling requirements that are ultimately imposed on manufacturers will have far-reaching implications on product liability litigation relating to biosimilars. For example, courts often examine a drug’s label to determine whether the warnings provided by a drug’s manufacturer were accurate or adequate. In this Draft Guidance, the FDA outlines that the safety and efficacy data presented in a biosimilar’s label should be derived entirely from clinical trials on the reference product (not the biosimilar product) unless the inclusion of data specific to the biosimilar product is necessary to inform safe and effective use by a health care practitioner. Biosimilar product manufacturers should heed this qualification in order to limit exposure to failure to warn claims down the road. Manufacturers should likewise continually—not just at the time a proposed label is initially submitted to the FDA—examine whether or not the inclusion of product-specific clinical data should be added to a label in order to ensure the information presented is accurate and adequate to inform the prescriber.

As currently written, the Draft Guidance also suggests that a pre-emption defense to certain product liability claims may not be available to biosimilar manufacturers. Generally, federal regulations mandate that generic small-molecule drugs employ the same labeling as their reference drugs, and thus federal law pre-empts failure-to-warn claims for generics. The Draft Guidance, however, states that biosimilar product manufacturers will be permitted to unilaterally change their labels in response to post-marketing adverse event reports. As such, attorneys for biosimilar manufacturers should not expect to be successful when asserting a preemption defense.


The Draft Guidance provides the FDA’s current position on a number of issues relating to biosimilar labeling, but those recommendations have not yet been adopted. Comments on the Draft Guidance were required to be submitted by June 3, 2016, and as outlined above, could have far-reaching implications on later product liability litigation.

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