Attorneys Analyze Biosimilar Labeling Guidance

FDA has again changed its mind on the question of whether a biosimilar’s labeling should identify itself as a biosimilar. That’s one of the takeaways attorney James Shehan (Hyman, Phelps & McNamara) sees in the FDA 3/31 guidance on biosimilar labeling. Writing in his firm’s FDA Law Blog, Shehan says that the guidance primarily affects the package insert, although a few sections affect patient labeling.

In the document, FDA lays out some general principles before proceeding to specific recommendations. The guidance makes detailed recommendations on treating clinical study data in biosimilar labeling that Shehan says appear to coincide with positions advocated by biosimilar applicants.

In its specific recommendations, the agency says that those sections of the biosimilar product labeling based on the reference-product labeling should be similar but need not be identical. Thus, differences in administration, storage, or safety information may require different labeling.

Shehan looks closely at the agency’s description of when biosimilar sponsors should use their biosimilar’s name, the reference product’s proprietary name, and the product’s “core name.” “While this part of the guidance appears to be logical,” he writes, “it may result in labeling that is confusing to users, considering that the labeling will apparently switch back and forth between three different names to make distinctions whose subtlety may escape a busy or uninformed end user.”

According to Shehan, the guidance provision that may generate the most discussion calls for labeling of biosimilar products to identify the products as biosimilars. FDA had included that provision in a 2012 draft guidance but then deleted it from the 2015 finalized version. Now, he says, it is reinstated in this guidance.

Attorneys Joanne Hawana and Lauren Moldawer (Mintz Levin) discuss stakeholder concerns about the 2015 final labeling package for Sandoz’ Zarxio (filgrastim-sndz) because that labeling was essentially identical to that for the reference product, Amgen’s Neupogen. “Therefore,” they write, “a key aspect of the newly issued draft guidance is the extent to which biosimilar labeling should be consistent with the label of the reference product. FDA is not requiring biosimilar labels to be identical to its reference product; however, it proposes that biosimilar labels should heavily rely upon their reference products.”

The two also say that the required biosimilarity statement may come as a relief to biological manufacturers and other stakeholders who raised concerns that labeling may not clearly state that the product has been approved through the abbreviated 351(k) pathway.

Finally, attorneys Jacob Siegel and Irena Royzman (Patterson Belknap) say the draft guidance continues to treat biosimilars like generics. “As with generic labeling,” they write, “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 modification.”

In the guidance, according to the post, “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 healthcare 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.”

In a departure from the label for Zarxio, where the core nonproprietary name was used in describing the data for the innovator product, the two write, the agency now recommends 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. However, FDA says that biosimilar names 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 should also be used in describing information specific to the biosimilar such as dosage information or storage and handling. If the label contains risk information that applies generally to the innovator product and the biosimilar, the attorneys say, the agency recommends using the core nonproprietary name plus the word “products.”

This analysis also notes that while the labeling guidance does not expressly address nonproprietary names for innovator and biosimilar biologics, which is the subject of a different draft guidance, its naming examples in this guidance suggest that FDA may stay with its proposed approach of using meaningless distinguishable nonproprietary names in its anticipated final guidance on nonproprietary naming.