One and Done: Federal Circuit Affirms No New Notice Requirement Under BPCIA for Supplement to aBLA That Does Not Alter Biosimilar Structure

Overview

On July 6, 2020, the Federal Circuit affirmed denial of Genentech’s motions to enjoin Amgen from marketing MVASI™ (bevacizumab-awwb), a biosimilar version of Genentech’s AVASTIN® (bevacizumab), an anti-angiogenic agent indicated for treating metastatic colorectal cancer in combination with certain other chemotherapies. The Federal Circuit held that filing a supplement to a previous biosimilar application does not trigger new notice requirements unless the biologic itself has changed. Both the district court and the Federal Circuit focused on the statutory language of the Biologics Price Competition and Innovation Act (“BPCIA”), particularly the relationship between § 262 (l)(8)(A) “Notice of Commercial Marketing” (“subsection (l)(8)(A)”) and § 262 (k) “Licensure” (“subsection (k)”). The Federal Circuit concluded that changes made under subsection (k) that do not alter the biosimilar’s chemical or biological structure do not require new notice under subsection (l)(8)(A).

Statutory Requirements

The BPCIA aims to balance the competing interests of original developers of biologics (or innovators), which make substantial investments of time and capital to develop a new biologic, and those of biosimilar manufacturers, which provide patients with lower cost options for biologics. The BPCIA awards innovators a twelve-year period of market exclusivity for an approved biologic, beginning the date the biologic becomes licensed. After the exclusivity period expires, a biosimilar manufacturer may market a competing biosimilar upon Food and Drug Administration (“FDA”) approval and only after the biosimilar provides sufficient notice to the original developer, as required under the BPCIA.

The facts of the case involve two BPCIA provisions under 42 U.S.C. § 262, namely subsection (k) and subsection (l)(8)(A). Under subsection (k), a biosimilar company may submit an application (known as an abbreviated biologics license application or “aBLA”) to the FDA for licensure of a biological product based on information evidencing that the product is biosimilar to a reference product  Under subsection (l)(8)(A), the aBLA applicant shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k),” (i.e., Notice of Commercial Marketing).

Factual Background

Following FDA approval in 2004, Genentech marketed their biologic, bevacizumab, as AVASTIN®. After the twelve-year exclusivity period expired in November 2016, Amgen filed an aBLA under subsection (k) with the FDA for approval of its biosimilar version of bevacizumab, MVASI™. As part of the aBLA, Amgen identified Amgen’s Thousand Oaks, California facility as the manufacturing location for MVASI™. The FDA approved Amgen’s aBLA in September 2017. Subsequently in October 2017, Amgen sent its “Notice of Commercial Marketing” letter pursuant to subsection (l)(8)(A) to Genentech indicating intent to commence marketing MVASI™ after 180 days.

Amgen submitted four supplements to its aBLA, the third and fourth of which are discussed by the court. The third-submitted supplement added a manufacturing location for MVASI™, and the fourth-submitted supplement modified the drug’s label. The FDA approved these supplements in December 2018 and June 2019, respectively.

District Court Procedural History

Genentech filed “an emergency motion and a motion for a temporary restraining order” in March 2019 in district court based on Amgen’s alleged “failure to comply with the notice requirement” of subsection (l)(8)(A). Genentech was seeking to block Amgen from commercially marketing its biosimilar until adequate notice under subsection (l)(8)(A) was provided and the requisite 180 days had elapsed. Genentech argued that Amgen’s third and fourth supplements to its aBLA resulted in new and distinct applications that require new notices under Section 262(l)(8)(A).

Genentech’s Argument

Genentech argued that Amgen’s October 2017 letter failed to satisfy subsection (l)(8)(A)’s notice requirement because the MVASI™ product approved by the FDA in September 2017 was materially changed when the FDA approved Amgen’s third and fourth supplements in June 2019. Genentech claimed that any product marketed pursuant to the June 2019 approval was “a distinct ‘product licensed under subsection (k)’ requiring its own (l)(8) notice” because such a product was “made by a new manufacturing process, accompanied by a new label, and the subject of separate applications, FDA reviews, and FDA approvals.” Genentech stated that under subsection (k), a biologic’s “manufacturing facilities and labeling” are “requirements [that] define a biological product.” Genentech asserted that changes to manufacturing locations or labeling necessarily change the definition of the biological product.

District Court’s Analysis

The court rejected Genentech’s arguments, and instead found that: (1) the FDA had the authority to approve Amgen’s final two supplements to the original aBLA, which changed manufacturing facilities and labelling specifications; (2) the MVASI™ product that was subject to the original aBLA was chemically and biologically the same as the product which was subject to supplemental filings; (3) the MVASI™ product had been “licensed under subjection (k)” since September 2017; and (4) Amgen’s October 2017 notice letter satisfied subsection (l)(8)(A).

The court focused its analysis on the language of the BPCIA. Specifically, subsection (k)(3) states that the FDA “shall license the biological product under [subsection (k)]” if, in the process of reviewing “an application” or “a supplement to an application,” the FDA determines that information submitted is sufficient to demonstrate that the proposed biosimilar is safe and effective. The court interpreted this language to mean that only one biologic product (i.e., one that is chemically and biologically the same) could be the subject of an application and supplements to that application. Accordingly, the court reasoned that because MVASI™ was disclosed in the original application, and Amgen’s supplements did not alter MVASI™’s chemical or biological structure, Amgen’s supplements to its aBLA did not transform the disclosed MVASI™ into a different product requiring new notice to Genentech under subsection (l)(8)(A).

The court also identified three other subsections of the BPCIA to support its analysis. First, the express definition for a “biological product” within § 261(i)(1) does not include identifying a manufacturing facility for making the biological product nor does it include any requirements for a product label. Second, the court pointed to § 262 (k)(2)(A)(i)(V), which refers to “the facility in which the biological product is manufactured,” and to § 262(b), which makes it illegal to “falsely label” a biological product, as express distinctions juxtaposing the definition of a biological product with references to manufacturing sites and labeling requirements. Third, the court relied on § 262 (k)(7) which prohibits the FDA from approving biosimilars “until the date that is 12 years after the date on which the reference product was first licensed.” Given that the court found no change in the structure of the biological product, and that Amgen’s MVASI™ was properly licensed more than twelve years after Genentech’s Avastin (i.e., after expiration of the market exclusivity period), the court decided against enjoining Amgen from marketing MVASI™. Genentech appealed to the Federal Circuit.

Federal Circuit’s Decision

The Federal Circuit noted that the statutory language in subsection (l)(8)(A) “makes clear that the biosimilar applicant must provide notice to the reference product sponsor prior to commercially marketing the biological product.” Like the district court, the Federal Circuit relied on § 262(i)(1) to define a “biological product” as something that is chemically and biologically the same as the reference product, not something tied to a manufacturing location or label. The court noted that subsection (k), not subsection (l)(8)(A), details the requirements for licensure. Subsection (l)(8)(A) requires only notice of commercial marketing of the “biological product.” The court noted that the language of this subsection makes no reference to subsection (k). In the court’s words, “[s]ection 262(l)(8)(A) relates to timing.”

The Federal Circuit supplemented their analysis of the plain language within the statutory text by deferring to the Supreme Court’s decision in Sandoz Inc. v. Amgen Inc., 137 S. Ct. 1664 (2017), in which the Supreme Court explained that the term “licensed” in subsection (l)(8)(A) means that a product should be licensed by the date of the first commercial marketing, not that each supplemental application requires new notice obligations. The Supreme Court held that “nothing in § 262(l)(8)(A) turns on the precise status or characteristics of the biosimilar application.” Further, the Supreme Court explanation that subsection (l)(8)(A) contains a single timing requirement—that applicants must provide notice at least 180 days prior to marketing a biosimilar—supported the Federal Circuit’s own finding that subsection (l)(8)(A)’s notice requirement was separate from subsection (k)’s licensure requirements. Accordingly, the Federal Circuit affirmed the district court’s decision to deny Genentech’s motions to block MVASI™ from being marketed.

(Co-authored by Claire Schuster)