On March 31, the U.S. Food and Drug Administration (FDA) published its long-awaited draft guidance, “Labeling for Biosimilar Products.” While the draft guidance does require a prominent labeling statement identifying a product as a biosimilar, FDA otherwise appears to rely on the generic drug model in designing biosimilar labeling that is as similar as possible to the reference product labeling. 

The draft guidance effectively rejects arguments that biosimilar labeling should include clinical data regarding the biosimilar or other information thought to be important to healthcare providers. For instance, FDA makes it clear that biosimilar labeling need not include statements indicating whether the biosimilar is licensed for all, or fewer than all, of the reference product’s conditions of use; nor must biosimilar labeling disclose whether the biosimilar’s conditions of use were licensed based on extrapolation. The draft guidance also actively discourages biosimilar developers from including in labeling any information regarding the type or extent of data used to support FDA’s biosimilarity determination. Labeling regarding interchangeability is not discussed and left to a future guidance. 

The Draft Guidance

The Biologics Price Competition and Innovation Act, Pub. L. No. 111-148, §§ 7001-7003, 124 Stat. 119, 804-21(2010), provides that a biosimilarity determination means that “there are no clinically meaningful differences between the proposed product and the reference product in terms of safety, purity, and potency.” FDA relies on this language to conclude that a biosimilar product’s labeling should be based on “relevant data and information from the reference product labeling” with only limited “appropriate product-specific modifications” necessary for “the safe and effective use of the biosimilar product.” Draft guidance at 3, 5.

In support of this approach, the draft guidance identifies three categories of information to be included in biosimilar labeling. The first category comprises information from the reference product’s labeling. The second is information intended to communicate that there are “no clinically meaningful differences” between the biosimilar and the reference product. This includes the “biosimilarity statement” in the Highlights section of the labeling, which would identify the drug as a biosimilar, identify the reference product and incorporate a definition of biosimilarity. Third is limited informationspecific to the biosimilar, provided that this information is “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.” Draft guidance at 5.

The draft guidance makes it clear that the scope of the third category (i.e., biosimilar-specific information) is narrow and does not include studies conducted for licensure: “[a]s a general matter, it is FDA’s view that biosimilar product should not include a description of [data from a clinical study of a proposed biosimilar product], given that a clinical study supporting the licensure of the biosimilar product generally would not be designed to independently demonstrate the safety and efficacy of the product ....” Draft guidance at 3 (emphasis added). 

According to FDA, limiting the third category is necessary to avoid confusion on the part of healthcare practitioners regarding the status and meaning of biosimilars. In a blog post about the draft guidance, Leah Christl, Ph.D., Associate Director for Therapeutic Biologics in the Center for Drug Evaluation and Research, states further that its approach is intended “to avoid potential confusion or misinterpretation” of clinical data regarding biosimilars, which in general “are not likely to be relevant to a healthcare provider’s prescribing considerations.”

To make clear whether information in the labeling pertains to the biosimilar, to the reference product or to both, the draft guidance provides a set of recommendations regarding when to use the biosimilar product’s trade name, the reference product’s trade name and the so-called “core name” (i.e., the portion of the nonproprietary name before the product-specific suffix described in prior FDA guidance). The result of these recommendations is that biosimilar labeling will refer to no fewer than three different drug names in the course of a single package insert.

Finally, the draft guidance expressly defers to future guidance “any specific recommendations for labeling for interchangeable biological products, including any interchangeability statement similar to the biosimilarity statement” in the draft guidance. Draft guidance at 12.

Broader Context

The draft guidance reflects a change in FDA’s approach to biosimilar labeling since the agency licensedits first biosimilar product, Zarxio, in March 2016. The labeling for Zarxio (filgrastim-sndz), a biosimilar referencing Neupogen (filgrastim), does not contain a statement indicating that the product is a biosimilar, nor does the labeling include the Neupogen brand name. On April 5, 2016, less than a week after the publication of the draft guidance, FDA licensed a second biosimilar, Inflectra (infliximab-dyyb), a biosimilar to Remicade (infliximab). Unlike Zarxio, the official labeling for Inflectra contains the biosimilarity statement and the reference product trade name.

Next Steps

FDA is soliciting comments on the draft guidance, including, specifically, the question of whether patient labeling should include a biosimilarity statement similar to the statement described in the draft guidance. Comments on the draft guidance should be submitted by June 3.