One of the FDA’s recent biosimilar guidance documents has drawn criticism for eliminating labeling information necessary for physicians to make prescribing decisions. The guidance document, titled, “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product,” was one of three released by the FDA in April 2015. These documents finalized drafts that were published for public comment in 2012. The finalized Scientific Considerations guidance document is non-binding, but describes the FDA’s current approach to biosimilar products.
The finalized Scientific Considerations guidance document is notable for what it leaves out. The 2012 draft document included specific guidance for the labeling of biosimilar products:
“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.”
The finalized document contains no such guidance, and the FDA has provided no explanation for its removal.
Similarly, FDA approved a label for the first approved US biosimilar, Sandoz’s Zarxio (filgrastim-sndz), which does not set forth the information FDA previously viewed as necessary for biosimilar labeling. The label for Zarxio does not state that the product is approved as biosimilar to Amgen’s Neupogen. It also does not state that the product has not been determined to be interchangeable to Neupogen. In addition, it does not identify the information provided by Sandoz to obtain approval for its product as a biosimilar, including information on immunogenicity specific to Zarxio.
The finalized FDA guidance and label for Zarxio have raised significant concern. In May, nine organizations representing physicians who routinely prescribe biologic medicines to their patients, including the American Association of Clinical Endocrinologists and American College of Rheumatology, sent a letter urging FDA “to ensure that biosimilar product labeling contains all needed data for physicians to make appropriate prescribing decisions for their patients.” In their letter, the physician associations stated that they were concerned that the label for Zarxio did not provide such information. They urged FDA to require a clear statement of biosimilarity and interchangeability previously described as “necessary” in the 2012 draft guidance. They also urged “FDA to give full consideration to what elements of the biosimilar data package would be helpful to physicians.” They explained that “given that a biosimilar – unlike a generic small molecule – has its own clinical data, there will likely be specific information from this data package that will help physicians, including the provision of information on immunogenicity, which can vary from the reference biologic.” They “urge[d] FDA not to employ a generic-like approach to labeling for biosimilars as it appears to have done with Zarxio.”
In a similar vein, this month, AbbVie, Inc., a biopharmaceutical company, submitted a citizen petition to the FDA, arguing that the FDA’s new approach to biosimilar labeling is contrary to the BPCIA. In its petition, AbbVie states that “[b]iosimilars are not generic drugs and should not be labeled like generic drugs.” AbbVie focuses on the approved labeling for Zarxio, which lacks information that FDA identified as “necessary” for an approved label in its 2012 draft guidance. AbbVie states that the labeling for Zarxio, which has not been found interchangeable with Amgen’s Neupogen, is “nearly identical” to the approved labeling for Neupogen and nowhere states that Zarxio is not interchangeable to Neupogen, indicating that the FDA decided to apply the “same labeling” requirement for generic small-molecule drugs to biosimilars.
AbbVie contends that it would be “legally unsound” for the FDA to adopt a “same labeling” approach to biosimilars. First, the BPCIA does not include the “same labeling” requirement applicable to generic drugs and recognizes that biosimilars are inherently different from their reference products. Second, this approach would result in labeling that omits information necessary for safe and informed prescribing by physicians such as whether the product is interchangeable with the reference product and creates serious “misbranding issues” due to such omissions. Finally, AbbVie argues that FDA removed the labeling guidance in its 2012 draft from the finalized guidance document without providing the reasoned explanation required by the Administrative Procedure Act.
Similar to the requests made by physicians in their letter to FDA and FDA’s own 2012 draft guidance, AbbVie requests the FDA to require that biosimilar product labels contain: 1) a “clear statement that the product is a biosimilar, that the biosimilar is licensed for fewer than all the reference product’s conditions of use (if applicable), and that the biosimilar’s licensed conditions of use were based on extrapolation (if applicable);” 2) a “clear statement that the FDA has not determined that the biosimilar product is interchangeable with the reference product (if applicable);” and 3) a “concise description of the pertinent data developed to support licensure of the biosimilar, along with information adequate to enable prescribers to distinguish data derived from studies of the biosimilar from data derived from studies of the reference product.”