On August 10, AbbVie, Inc. filed a supplement to its earlier filed Citizen Petition, levying another challenge to FDA’s implementation of the Biologics Price Competition and Innovation Act (BPCIA). This supplemental filing specifically takes aim at FDA’s approach to biosimilar labeling, as evidenced in the FDA-approved labeling of the first biosimilar – Sandoz’s Zarxio® (filgrastim-sndz). AbbVie takes issue with the fact that Zarxio®’s FDA-approved labeling does not state that the product is a biosimilar and fails to note that Zarxio® is not interchangeable with the reference biologic – Neupogen®. This information, according to Amgen, is critical to ensuring informed prescribing and to omit this information makes the labeling misleading.

By way of background, the BPCIA establishes a pathway for follow-on biologics to obtain approval based upon a showing of “biosimilar[ity]” to a currently approved product. See 42 U.S.C. § 262(k). A product is “biosimilar” to a reference product if such product is “highly similar to the reference product notwithstanding minor differences in clinically inactive components” and “there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.” Data demonstrating biosimilarity must be derived from (i) analytical, (ii) animal studies (including the assessment of toxicity); and (iii) a clinical study or studies. Id. § 262((k)(2)(A)(i)(I)(aa)-(cc).

A biosimilar may also be deemed to be “interchangeable”, if a showing is made that the biosimilar “can be expected to produce the same clinical result as the reference product in any given patient,” and “for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy in alternating or switching between use of the [biosimilar] and the reference product is not greater than the risk of using the reference product without such alteration or switch.” Id. § 262(k)(4)(A)-(B). The first product that is found to be interchangeable with respect to a reference product is eligible for at least one year of exclusivity as against any other interchangeable product, and may also “be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.” Id. §§ 262(i)(3), (k)(6).

FDA’s potential or at least “placeholder” approach to biosimilar labeling was revealed in the approval of Zarxio® (see Zarxio® labeling here). As AbbVie notes, Zarxio®’s labeling does not state that the product is a biosimilar, nor does it state that the product has not been found to be interchangeable with the reference product. AbbVie asserts that this omitted information is critical to ensure informed prescribing. Indeed, as AbbVie points out, a since-revised FDA draft guidance indicated that a clear statement that the product has (or has not) been determined to be interchangeable is “necessary for a health professional to make prescribing decisions.” See FDA, Draft Guidance for Industry, Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, 20-21 (Feb. 2012), available here. Curiously, FDA issued a revised draft guidance prior to the approval of Zarxio® omitting this language.

AbbVie observes that FDA, in correspondence with the Senate Health, Education, Labor, and Pensions (HELP) Committee, indicated that the Purple Book (available here), contains the information AbbVie alleges should be included in the biosimilar labeling. See Letter from T. Kraus to L. Alexander et al., 2 (June 22, 2015). In FDA’s view, the Purple Book adequately informs prescribers of each biosimilar’s reference product and interchangeability determination. However, AbbVie acutely criticizes FDA for taking the position that “a material omission in the [labeling] for Zarxio . . . can be [cured] from another, non-labeling source.” Indeed, AbbVie describes FDA’s position as “indefensible” and contrary to “foundational principle[s] of FDA law.”

AbbVie also highlights various statements from both FDA and the Department of Justice (DOJ) made in the ongoing Amarin Pharma, Inc. v. FDA litigation (see blog post here) to argue that language is needed in the labeling of the biosimilar to distinguish data derived from studies of the biosimilar from data derived from studies to the reference product. For example, AbbVie cites a letter from Janet Woodcock to Amarin Pharma, Inc., stating that “to ensure that [statements] are not false or misleading, [FDA] recommend[s] that they [the statements] expressly disclose when studies were conducted using products other than [the product that is the subject of the statements].” See Letter from Janet Woodcock to Steven Ketchum, June 5, 2015, available here.

AbbVie’s supplement is another example of the efforts by both innovators and the generic industry to shape FDA’s implementation of the BPCIA. Other such efforts include the ongoing litigation between Sandoz and Amgen regarding the mandatory (or not) nature of the BPCIA “patent dance” (Federal Circuit decision here), and various citizen petitions and comments concerning the non-proprietary naming of biosimilars (see, e.g., GPhA’s Citizen Petition). As more blockbuster biologics lose patent protection in the coming years, including AbbVie’s Humira® (adalimumab), we expect to see more biosimilar applications being filed, along with more innovators seeking legal recourse to protect their market share. These early challenges will help shape the future of the biologics industry.