On December 2, 2020, Boehringer Ingelheim Pharmaceuticals, Inc. (“Boehringer Ingelheim”) submitted a Citizen Petition requesting a change in the FDA’s interpretation of “strength” of biological products under the Biologics Price Competition and Innovation Act (“BPCIA”). The Citizen Petition is available on regulations.gov under docket number: FDA-2020-P-2247. Boehringer Ingelheim seeks an interpretation of “strength” to mean total drug content, without regard to concentration. The Citizen Petition further requests the FDA update its guidance documents to incorporate the new definition, and apply the updated definition to pending and approved applications before the agency.

The proposed change would primarily impact the approval of “interchangeable” biological products. An “interchangeable” biological product “means that the biological product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” 42 U.S.C. § 262(i)(3). One requirement for the FDA to approve such a product is that the proposed biological product has the same “strength” as the reference product: “the route of administration, the dosage form, and the strength of the biological product are the same as those of the reference product; . . .” Id. § 262(k)(2)(i)(IV). According to Boehringer Ingelheim, the FDA currently interprets “strength” as encompassing both total drug content and concentration.

In the petition, Boehringer Ingelheim presents three arguments as to why the concentration should not be included when evaluating the strength of the biological product. First, Boehringer Ingelheim states that the FDA’s interpretation of “strength” conflicts with the BPCIA. Second, it unnecessarily and unreasonably facilitates anticompetitive practices, such as patent “evergreening” tactics designed to prevent or delay competition from biosimilar and interchangeable products seeking approval. And third, the interpretation is arbitrary and capricious in violation of the Administrative Procedure Act because it treats injectable solutions differently than similarly situated parenteral products without any reasonable basis.

Boehringer Ingelheim markets Cyltezo® in 20 mg and 40 mg doses, each administered at a 50 mg/mL concentration. Cyltezo is an approved biosimilar of Humira® at the same concentration. In addition to the original 50 mg/mL dosage, Humira was later approved for use in a 100 mg/mL formulation. Boehringer Ingelheim argues that when FDA interprets “strength” to mean concentration, it allows brand manufacturers to manipulate the concentration of their reference products at strategic times during the extended eight to ten-year development period for biosimilars, which unfairly creates a “moving target” for sponsors seeking approval via the 351(k) pathway. If the FDA modifies its interpretation of “strength” as Boehringer Ingelheim has requested, Boehringer Ingelheim can seek an interchangeability determination of Cyltezo that would apply to Humira’s higher concentration formulation.