Stakeholders urge FDA to retain interchangeability statements on biosimilar labeling

Two major pharmaceutical industry groups opposed the US Food and Drug Administration’s (FDA) proposal to remove details about interchangeability from product labels in its biologics labeling guidance. They assert that eliminating these statements would create confusion and that these labels are a major source of information for health care providers and prescribers.

Groups also complained that FDA’s plan to refer health care providers and prescribers to the Purple Book Database of Licensed Biological Products to obtain information about a product’s interchangeable status is not a feasible option.

FDA’s draft guidance document, which was issued in September 2023, is the first update of its labeling rules since 2018 (RELATED: Biosimilar labeling guidance suggests cutting interchangeability details from labels, Regulatory Focus 18 September 2023).

The major change from the 2018 guidance is FDA’s elimination of the interchangeability statement from the product labeling. FDA stated in a notice that “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.”

The agency said prescribers can consult the Purple Book if they have questions on approved biosimilar and interchangeable biosimilar products. The term interchangeable is defined by statute to mean that the product may be substituted for the reference product at the pharmacy level without the intervention of the prescriber.

In a recent blog post, Sarah Yim, director of FDA’s Office of Therapeutic Biologics and Biosimilars, justified the FDA’s proposal by saying that prescribers often don’t pay attention to interchangeability information when evaluating biosimilars (RELATED: Biosimilars: FDA offers rationale for dropping interchangeability designation, Regulatory Focus, 30 October).

FDA received 22 comments on the guidance. While most commenters opposed the elimination of the interchangeability statement, some biosimilar groups supported FDA’s proposal. The deadline for public comment closed on 17 November.

Retain the interchangeable labels

Two major pharmaceutical groups opposed FDA’s proposal to eliminate interchangeable designations on biosimilar labels.

The Biotechnology Innovation Organization (BIO) wrote that “the label is the main source of product information for patients, healthcare professionals (HCPs), including pharmacists, and the public in general.”

The group added that the Purple Book, which is available only via the FDA website, “is not routinely used by HCPs” and is not as “commonly recognized” as the product label.

BIO said this change may also lead to “unintended consequences,” such as implying that a biosimilar is interchangeable when it is not.

The Pharmaceutical Research and Manufacturers of America (PhRMA) also raised concerns about eliminating the interchangeability statement. FDA has already approved more than 40 biosimilars and many of those products include the interchangeable statement on their labeling. Discontinuing its use has the potential to “sow confusion,” according to PhRMA.

“Stakeholders who might not keep abreast of developments around Agency labeling guidance might view this differential labeling as significant and become confused as to the status of the various products, their relationship to one another, and the reason why the labeling differs from one product to another,” PhRMA commented.

The Alliance for Safe Biologic Medicines (ASBM), a group of stakeholders that includes physicians, pharmacists, patients, and manufacturers of both biologics and biosimilars, also urged FDA to retain the interchangeable statement.

“ASBM respectfully disagrees that the interchangeability statement is not valued by prescribing health care professionals,” the group wrote. “In a survey of 400 US physicians who prescribe biologics, participants were asked how important it is that the product label clearly indicates that a biosimilar is or is not interchangeable; approximately 80% of physicians rated the importance of this either a 4 or 5 on a 5-point scale. Likewise, a survey of over 400 pharmacists indicated that almost 90% of those polled rated the importance of the product label clearly indicating that a biosimilar is or is not interchangeable as a 4 or 5 on a 5-point scale.”

Elimination supported

Yet two biosimilar groups, the Biosimilars Council and the Biosimilars Forum, supported the elimination of the statement.

“The Purple Book is well-suited to relay information on biosimilarity and interchangeability,” the Biosimilars Council commented. “Removal of these statements from labeling also would align with generic drug labels, which do not include comparable statements or therapeutic equivalence ratings.”

The Biosimilars Forum agreed with FDA that the interchangeability statement would not be useful for prescribers, “who can prescribe either a biosimilar or an interchangeable biosimilar with equal confidence that they are as safe and effective as their reference products.”

The Forum also supported the agency’s recommendation to include interchangeability information in the Purple Book, since it is used as a pharmaceutical reference.

Public Comments

Stakeholders urge FDA to retain interchangeability statements on biosimilar labeling

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