Biosimilar labeling guidance suggests cutting interchangeability details from labels

In new draft guidance on biosimilar labeling, the US Food and Drug Administration (FDA) recommends removing details about interchangeability from the labels of these products, suggesting that the designation is confusing to prescribers and patients.

“[A] labeling statement noting that certain products within a 351(k) [Biologics License Application] have been approved as interchangeable, and explaining the interchangeability standard, is not likely to be useful to prescribers, who 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,” FDA said in the Federal Register announcement of the proposed changes.

The 20-page guidance document is the first update to “Labeling for Biosimilar and Interchangeable Biosimilar Products” since 2018, the FDA noted. If finalized, the new draft guidance will replace the 2018 document.

Since the agency approved the first biosimilar product 8 years ago, 40 new ones have come online, with the promise of many more to come. During that time, FDA said it “has gained valuable experience about labeling considerations for biosimilar and interchangeable biosimilar products, including labeling statements in the ‘Highlights of the Prescribing Information’ that explain biosimilarity and interchangeability.”

Sponsors who submit a single 351(k) BLA asking to license both biosimilar and interchangeable biosimilar products add to the confusion for clinicians and consumers, the FDA noted.

“Draft labeling for such applications would need to address both biosimilar and interchangeable biosimilar products, and the status of a particular product within such a BLA can change over time, for example, as relevant exclusivities expire. Determining how to appropriately label such products and keep labeling up to date without causing undue confusion has proven challenging,” FDA wrote.

A biosimilar may or may not be an interchangeable biosimilar, according to FDA. Section 351(i) of the Public Health Service Act defines “biosimilar” as a biological product that is highly similar to the reference product and without clinically meaningful differences in safety, purity, or potency. An interchangeable biosimilar must not only demonstrate biosimilarity to the reference product, it must also demonstrate (through switching studies) that it will produce the same clinical result as the reference product in any given patient and that switching between the two doesn’t cause any safety or efficacy issues.

Interchangeability is a big bonus for drugmakers, because these products can be substituted for the reference product at the pharmacy level, without needing a clinician’s approval. The FDA’s Purple Book Database of Licensed Biological Products already includes information on products that are approved as both biosimilar and interchangeable, and that is more useful to patients, pharmacists, physicians, and other health care providers than including that designation on the label, the agency argued in the Federal Register announcement.

“Consistent with this evolution in our thinking, the draft guidance states that both biosimilar and interchangeable biosimilar products should contain the same biosimilarity statement in the Highlights of the Prescribing Information. This statement is applicable to biosimilar and interchangeable biosimilar products,” the agency wrote.

The decision also affects the guidance’s supplemental question-and-answer document, the FDA said, noting that it has withdrawn questions and answers about including an interchangeability statement in the labeling of products licensed as interchangeable.

The FDA is particularly interested in hearing from drugmakers about this proposal. “Specifically, FDA invites comment on how useful such biosimilarity statements have been for healthcare practitioners and the public, whether such statements can be improved to provide more clarity on what biosimilarity means, and whether biosimilar and interchangeable biosimilar product labeling should include such a statement at all,” the agency wrote.

The draft document also touches on labeling pediatric indications for biosimilars, incorporating immunogenicity data, and how to refer to supporting clinical trials that reference products not approved in the United States.

The labeling should make it clear if a non-US approved product was used in any way to support the US-approved biosimilar, the draft noted.

If the reference product labeling contains information on immunogenicity, then the biosimilar product needs to incorporate that. FDA suggested that an explanatory disclaimer paragraph should appear directly before that information and provided a template for this: “The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies.”

For pediatric use labeling, the draft guidance recommends that sponsors first label the biosimilar as safe or unsafe, then refer to pediatric safety data for the reference product, and then restate and elaborate upon that information using the biosimilar’s name.

Comments will be accepted on regulations.gov through 18 December 2023 using the docket number FDA-2016-D-0643.

Draft guidance

Biosimilar labeling guidance suggests cutting interchangeability details from labels

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