FDA Issues Draft Guidance on Labeling for Biosimilar Products, With Potential Implications for Litigation

Biosimilar News  •  BPCIA and Related U.S. Statutes  •  Regulatory Guidances  •  U.S. FDA News

Last month, the FDA released draft industry guidance on Labeling for Biosimilar Products.  The draft guidance provides FDA’s labeling recommendations for applicants seeking approval to market biosimilar products and applies only to non-interchangeable product.

The draft guidance describes the FDA’s expectations about what information biosimilar manufacturers should include in their labels and how similar biosimilar labels need will be to their RLP counterparts.  The new guidance departs somewhat from the “same labeling” approach that the FDA previously took when working with Sandoz toward the approval of Zarxio®, the first biosimilar licensed under the BPCIA.  Unlike the Hatch-Waxman Act, which governs FDA approval of generic conventional small-molecule drugs, the BPCIA does not contain a “same labeling” provision that requires biosimilar drugs to have essentially identical information in their labels as the branded reference listed product (“RLP”).  The FDA’s choice to use the “same labeling” approach for Zarxio® has been the subject of significant debate, with many supporters and dissenters in the pharmaceutical industry (see here, here, here and here).

Highlights from the FDA’s Draft Guidance

  • Biosimilar product labeling should include a description of the clinical data that supported safety and efficacy of the RLP “as described in the FDA-approved product labeling for the reference product.”
  • Biosimilar labeling should generally not include a description of data from clinical studies of the biosimilar product unless “necessary to inform safe and effective use by a health care practitioner.  The FDA explained that clinical studies supporting licensure of biosimilars generally would not independently demonstrate safety and efficacy or support approval, but rather only demonstrate that “there are no clinically meaningful differences” between the biosimilar product and the RLP.  Data from clinical studies designed to demonstrate biosimilarity are therefore not likely to be relevant to a physician’s “considerations regarding safe and effective use of the biosimilar product” and are likely to “cause confusion.”
  • Text based on RLP labeling need not be identical “and should reflect currently available information necessary for the safe and effective use of the biosimilar product.”  The draft guidance explains that differences between the RLP and biosimilar product label could reflect information specific to the biosimilar product, including “differences such as administration, preparation, storage, or safety information that do not otherwise preclude a demonstration of biosimilarity.”
  • The draft labeling includes guidelines for use of product names in biosimilar product labeling, including when to refer to the RLP brand name, when to use the biosimilar brand name (if any), and when to use the “core name” (the name of the biologic component shared by the RLP and biosimilar).
  • If a biosimilar manufacturer is not seeking approval for all indications for which the RLP is approved, the biosimilar product need not include in its label certain information from the RLP label related to indications that are not being sought. However, information that is necessary to “ensure safe use” may be required, even if related to indications not sought by the biosimilar manufacturer. The information that may be required mostly relates to safety information, and including several specified sections of the label: BOXED WARNING, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS, DRUG INTERACTIONS, and USE IN SPECIFIC POPULATIONS.
  • The draft labeling recommends that a biosimilar product’s label include a “biosimilarity statement” stating that the biosimilar product is biosimilar to the RLP for the listed indications, and defining “biosimilar” to mean 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.”  Notably, Celltrion’s recently approved label for Inflectra® includes this recommended biosimilarity statement, but Sandoz’s label for Zarxio® does not include a biosimilarity statement or otherwise refer to the RLP.
  • The recommendations explicitly do not apply to interchangeable products.  The draft guidance states that “[a]ny specific recommendations for labeling for interchangeable biological products, including any interchangeability statement similar to the biosimilarity statement …, will be provided in future guidance.”

Implications for Litigation

The new draft guidelines have some important implications for litigations involving biosimilar products, including both patent litigation and products liability litigation.

Patent Litigation: In Hatch-Waxman cases for generic drugs, a generic manufacturer’s label, together with the rest of its Abbreviated New Drug Application, limits what the generic manufacturer can market and is often dispositive of the issue of infringement.  The possibility that a biosimilar product can have substantively different labeling than the RLP  may complicate the infringement analysis in BPCIA litigations, with the potential to weaken or strengthen an infringement case, depending on the situation.  For example, if a biosimilar manufacturer can satisfy the FDA while avoiding language that implicates infringement of patents covering the RLP, they may be able to gain an advantage in litigation. On the other hand, because biosimilar manufacturers, unlike generic drug manufacturers, have the ability to substantively modify their labels and to actively market their products, it may be more difficult for biosimilar manufacturers to dodge allegations of induced infringement of method of use claims.

Products Liability Litigation: In 2011, the Supreme Court held in PLIVA, Inc. v. Mensing that the statutory requirement that generic products approved under the Hatch-Waxman Act carry the same labeling as the RLD shields generic manufacturers from products liability claims based on state-law duties to properly warn consumers. The Supreme Court found that generic manufacturers were stuck between the federal requirement to provide the same information as the RLP manufacturer in the label and other communications with physicians and patients, and state-law requirements to provide adequate warnings about a product’s dangers. Under these circumstances, the Court held that federal law preempts state law, and generic manufacturers cannot be held liable for communications they cannot control.  It remains to be seen how, if at all, the FDA’s draft biosimilar labeling guidance may affect the availability of Mensing preemption to manufacturers of biosimilar products as a defense to state-law tort claims.

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