By Sarah Yim, M.D., director of the Office of New Drugs’ Office of Therapeutic Biologics and Biosimilars
Over the last eight years, FDA has approved more than 40 biosimilar products (biosimilars), and they have become an important treatment option for health care professionals and their patients. We have also gained valuable experience about labeling considerations for biosimilar and interchangeable biosimilar products (interchangeable biosimilars). The recommendations in our draft labeling guidance reflect this experience and have been revised to specifically include interchangeable biosimilar products.
A biosimilar is highly similar to a biologic medication already approved by FDA – called the reference product. Biosimilars have no clinically meaningful differences in terms of safety, purity, and potency from the reference product. This means you can expect the same safety and effectiveness from the biosimilar over the course of treatment as you would from the reference product.
An interchangeable biosimilar is a biosimilar that may be substituted without consulting the prescribing health care professional. This practice is called “pharmacy-level substitution” and is subject to state law.
Both biosimilars and interchangeable biosimilars must meet the same high standard of biosimilarity for FDA approval, and both are as safe and effective as the reference product. Additionally, because biosimilars can be prescribed in place of the reference product in the marketplace once approved, prior to a biosimilar’s approval FDA considers whether doing so would raise safety or efficacy concerns.
New Recommendations for the “Biosimilarity Statement” in Biosimilar and Interchangeable Biosimilar Product Labeling
Previously, we recommended that Prescribing Information (labeling) include a “Biosimilarity Statement” or “Interchangeability Statement” describing the product’s relationship to its reference product in the Highlights section. As an example (using fictitious names), the biosimilarity statement would be: NEXSYMEO (replicamab-cznm) is biosimilar to JUNEXANT (replicamab-hjxf). The interchangeability statement would be: NEXSYMEO (replicamab-cznm) is interchangeable to JUNEXANT (replicamab-hjxf). However, after many years of experience, FDA is recommending that all labeling for biosimilars, including interchangeable biosimilars, include one statement - a “biosimilarity statement”. There are several reasons we recommend that the labeling include a biosimilarity statement for all biosimilars regardless of whether the biosimilar is approved as interchangeable.
The Prescribing Information is written for health care professionals, and its primary purpose is to contain a summary of the essential scientific information needed for the safe and effective use of the product. Information about interchangeability is relevant to substitution at the pharmacy. We believe that statements in the Prescribing Information identifying that products have been approved as interchangeable with the reference product and describing the interchangeability standard are not necessary for informing the safe and effective use of the product to prescribing health care professionals. Information about which products are licensed as interchangeable is located in FDA’s Purple Book: Database of Licensed Biological Products.
Moreover, as we gain more experience with licensing biosimilar and interchangeable biosimilar products, we are finding that a single biosimilar application and associated Prescribing Information may include both biosimilar and interchangeable biosimilar products at the same time. We have considered multiple approaches to accommodate this scenario, some of which raised a variety of concerns, including increased confusion. Including biosimilarity statements in the Prescribing Information for both biosimilar and interchangeable biosimilar products is factually accurate and avoids these concerns.
In addition, there may be inaccurate perceptions that interchangeable biosimilars are safer or more effective than biosimilars that are not approved as interchangeable. The interchangeability designation does not indicate a higher level of biosimilarity. Health care professionals can prescribe both biosimilar and interchangeable biosimilar products in place of the reference product with equal confidence that they are as safe and effective as their reference products. Including biosimilarity statements in the Prescribing Information for both biosimilar and interchangeable biosimilar products may avoid confusion among health care professionals about the significance of FDA’s determination that a biosimilar is interchangeable with the reference product.
FDA is seeking public comment on the usefulness of biosimilarity statements in the Prescribing Information.
General Biosimilar Labeling Recommendations
FDA recommends that biosimilar and interchangeable biosimilar product labeling incorporate relevant data and information from the reference product labeling, with appropriate modifications. The relevant data and information from the reference product labeling that should be incorporated into the biosimilar and interchangeable biosimilar product labeling will depend on whether the applicant is seeking licensure for all conditions of use (e.g., indication(s), dosing regimen(s)) or fewer than all conditions of use for which the reference product has been previously licensed. In addition, biosimilar and interchangeable biosimilar product labeling may include information specific to the biosimilar or interchangeable biosimilar product that is necessary to inform safe and effective use, including preparation, administration, and storage conditions. This information may differ from that of the reference product labeling to reflect differences between the biosimilar or interchangeable biosimilar product and the reference product.
Prescriber and Pharmacist Impact
Prescribers can prescribe both biosimilar and interchangeable biosimilar products in place of the reference product with equal confidence that they are as safe and effective as their reference products.
Our updated guidance will not impact pharmacy-level substitution of interchangeable biosimilar products. Not including an interchangeability statement in the product’s Prescribing Information does not change the status of the product or mean that the product is not interchangeable.
Because interchangeability pertains to pharmacy-level substitution, it is more appropriate to include information about interchangeability in the Purple Book, which may be easier to use as a pharmaceutical reference, rather than in product labeling, which is prescriber-focused.
For more information about biosimilars, visit the FDA Biosimilars page.