On September 15, 2023, the Food and Drug Administration (FDA) released draft guidance entitled “Labeling for Biosimilar and Interchangeable Biosimilar Products.”1 The agency is accepting comments through November 17, 2023, and the finalized guidance will revise and replace the 2018 guidance for the industry entitled “Labeling for Biosimilar Products.”

The draft guidance contains 2 important takeaways: First, both biosimilar and interchangeable biosimilar products should contain the same biosimilarity statement in the “Highlights of the Prescribing Information.” Second, the FDA has recommended to the requirement for an interchangeability statement in the labeling of products licensed as interchangeable within the “Additional Draft Q&As.”

While this is potentially a significant move for the FDA, interchangeability designation appears to be less important for Health Care Provider (HCP) administered products. Medical policy decision makers have been more willing to embrace biosimilars because of their ability to reduce costs and dependence on rebates for medical benefit drugs tends to be less than on the pharmacy benefit. In addition, the HCP is both prescribing and administering the biosimilar. Since the provider is, in essence, already substituting the biosimilar for the reference product, the pharmacy or payer is not required to obtain approval from the provider.

The concept of interchangeability is more impactful for self-administered pharmacy benefit biosimilars, which only recently became available. The FDA states that an interchangeable product may be substituted for the reference product by the pharmacy without the involvement of the prescriber2 only when permitted by state laws.3 While many states allow a pharmacist to change from a reference product to a biosimilar, notification to the provider and/or member may still be required, introducing an extra step in the dispensing process and an increase in operational costs.

It seems like the FDA is leaning towards labeling all licensed biosimilars as interchangeable, similar to how the European Medicines Agency views biosimilars.4 By doing so, the FDA is acknowledging that interchangeability designation does not indicate a higher level of biosimilarity, safety, or efficacy. If the proposed labeling updates to biosimilars are finalized and implemented, it may be a game changer for pharmacy benefit products. Removing interchangeability designation could mitigate some of the challenges with biosimilar adoption by removing access barriers. As a result, there may be more incentives for payers to cover or prefer multiple biosimilars rather than having a “pick one or two biosimilar” strategy along with covering the reference product. Removing interchangeability requirements and having the states adopt this ideology in their substitution laws can help biosimilar manufacturers compete. It will promote an environment where substitution is permissible, similar to generics with traditional drugs. For a reference product manufacturer, however, there is a downside: Their ability to maintain market share after a biosimilar launch may lessen to that of a small molecule product market share after loss of exclusivity (LOE).

Regardless, manufacturers should understand how the potential label updates may impact the biosimilar space including R&D, state law, prescribing, dispensing, and payers. Proactively communicating their product attributes and value will be the key to success. Here are 3 ways that biosimilar manufactures can ensure pull through of the potential FDA label update:

  1. Creating above-brand educational pieces highlighting the value of biosimilars and FDA ideology around interchangeability for pharmacists and payers
  2. Developing a cost-consequence or budget impact model for access decision makers
  3. Drafting branded pieces that communicate information on unique attributes of their biosimilar product

In conclusion, potential FDA changes to interchangeability will have a big impact on self-administered products, and all manufacturers with either biosimilars or reference products may benefit by preparing for possible implementation.


  1. US Labeling for Biosimilar and Interchangeable Biosimilar Products. FDA. September, 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/labeling-biosimilar-and-interchangeable-biosimilar-products
  2. Biological Product Definitions. FDA. https://www.fda.gov/files/drugs/published/Biological-Product-Definitions.pdf
  3. Cardinal Health. Biosimilar Interchangeability Laws. 2021. https://www.cardinalhealth.com/content/dam/corp/web/documents/publication/Cardinal-Health-Biosimilar-Interchangeability-Laws-by-State.pdf
  4. European Medicines Agency. Biosimilar medicines can be interchanged. September 19, 2023. https://www.ema.europa.eu/en/news/biosimilar-medicines-can-be-interchanged#:~:text=EMA%20and%20the%20Heads%20of%20Medicines%20Agencies%20%28HMA%29,their%20reference%20medicine%20or%20with%20an%20equivalent%20biosimilar