On Thursday, FDA released draft guidance clarifying its position on labeling biosimilar products. While the guidance addresses some of the concerns raised by physicians and industry, FDA’s guidance mostly continues to treat biosimilars like generics. As with generic labeling, FDA takes the position that a biosimilar label should largely incorporate the information from the innovator product labeling, though the guidance does provide for certain product-specific modifications.
FDA’s labeling guidance has been long awaited. The label for Sandoz’s Zarxio, the first approved US biosimilar, raised concern from physicians and industry about labeling of biosimilars. Zarxio’s label did not state that it was approved as a biosimilar of Amgen’s Neupogen, nor did it state that Zarxio is not interchangeable with Neopogen. The label was in stark contrast to FDA’s 2012 draft scientific considerations guidance, which described such information as “necessary” for physicians to make prescribed decisions:
Labeling of a proposed product should include all the information necessary for a health professional to make prescribing decisions, including a clear statement advising that:
• This product is approved as biosimilar to a reference product for stated indication(s) and route of administration(s).
• This product (has or has not) been determined to be interchangeable with the reference product.
Shortly after the approval of Zarxio in March 2015, this guidance was removed from the finalized scientific considerations guidance document and FDA promised to issue a specific labeling guidance. In yesterday’s draft labeling guidance, FDA takes a middle ground position. It recommends stating in the label that a biosimilar product is biosimilar to an innovator product, a so-called “biosimilarity statement,” but not that it has not been determined to be interchangeable with the innovator product. The recommended biosimilarity statement reads 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 refers to the below footnote:
*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.
The label for Zarxio was also essentially identical to that of Amgen’s Neupogen although biosimilars, unlike generic drugs, are not copies of innovator products. In its guidance, FDA takes the position that it is generally inappropriate for the biosimilar label to contain information and data from a clinical study of the proposed biosimilar, given that a study supporting a biosimilar application is “not likely to be relevant to a health care practitioner’s considerations regarding safe and effective use.” Rather, according to FDA, the label should include a description of the clinical data demonstrating the safety and efficacy of the innovator product, as described in the label for the innovator product.
FDA does recommend using the name of the innovator product rather than the name of the biosimilar or the core nonproprietary name in describing the clinical studies and data for the innovator product. This is a departure from FDA’s label for Zarxio, where the core nonproprietary name was used in describing the data for the innovator product. In this way, FDA attempts to address the misapprehension that the data in the label of the biosimilar product comes from studies using the biosimilar product.
FDA explains that biosimilar names, by contrast, should be used in “directive statements” and “recommendations for preventing, monitoring, managing or mitigating risks” such as directions to discontinue use of the biosimilar in patients with a particular adverse reaction. Biosimilar names are also to be used in describing information specific to the biosimilar such as dosing information or storage and handling. Where the label concerns risk information that applies generally to the innovator product and the biosimilar, FDA recommends a third convention: the use of the core nonproprietary name plus the word “products.” For instance, a label for a biosimilar of Amgen’s Neupogen (filgrastim) would refer to the risks of treatment with “filgrastim products.”
FDA notes that its guidance is only for biosimilar products and that it continues to consider the types of data and information that would support a demonstration of interchangeability. FDA states that it will provide any specific recommendation for labeling interchangeable biologic products in future guidance.
Also of note, while the labeling guidance does not expressly address nonproprietary names for innovator and biosimilar biologics, the subject of a different draft guidance, its naming examples suggest that FDA may stay with its proposed approach of using meaningless distinguishable nonproprietary names in its anticipated final guidance on nonproprietary naming. In the draft guidance, FDA proposed using a nonproprietary name followed by a dash and a suffix of four random letters. In a flood of comments, most stakeholders expressed concern over using meaningless names and innovator companies and biosimilar manufacturers alike voiced their preference for meaningful and memorable distinguishable suffixes to the meaningless ones proposed by FDA. In its labeling guidance, however, FDA makes use of its proposed naming scheme. It uses “replicamab-hjxf” as an exemplary nonproprietary name for the innovator product and “replicamab-cznm” for the biosimilar.
As with its earlier draft guidances, FDA invites comments from industry, health care providers and patients.
