Food & Drug Administration/FDA Archives

Patent Law Principles Apply to Claim Scope: Orange Book Delisting and Listing and Regulations

The US Court of Appeals for the Federal Circuit ordered that the only Orange Book patent asserted in a lawsuit must be delisted since its claims were directed to the computer-implemented distribution system and not a method of use. Jazz Pharms., Inc. v. Avadel CNS Pharms., LLC, Case No. 23-1186 (Fed. Cir. Feb. 24, 2023) (Lourie, Reyna, Taranto, JJ.)

Jazz Pharmaceuticals holds a new drug application (NDA) for Xyrem, an oral sodium oxybate solution prescribed to help those with certain narcolepsies manage cataplexy. Sodium oxybate itself is no longer covered by patents because it has been used in relation to narcolepsy since the 1960s. For this reason, Jazz built its patent portfolio around Xyrem’s formulation, use and distribution.

Jazz uses a single-pharmacy distribution system for Xyrem, known as a risk evaluation mitigation strategy (REMS). Implementing REMS was a condition of Xyrem’s US Food & Drug Administration (FDA) approval because it mitigates safety risks of dangerous active pharmaceutical ingredients such as sodium oxybate. One of Jazz’s patents is directed to this REMS distribution system. Abbreviated New Drug Application (ANDA) 505(b)(2) NDA (Hybrid NDA) approval is similarly conditioned on implementing a REMS that is sufficiently comparable to any that the NDA holder must implement. The FDA eventually determined that single-pharmacy systems were unnecessary for Xyrem and potentially detrimental.

Avadel submitted a hybrid NDA for a drug that requires only a single nightly dose, unlike Xyrem, which requires a patient to wake up during the night to ingest a second dose. Avadel’s application also proposed a more lenient REMS that utilizes multiple pharmacies. In view of these differences, Avadel believed that it could avoid a lengthy FDA approval process because all of Jazz’s Xyrem Orange-Book-listed patents seemed addressable without making any Paragraph IV certifications. As for the REMS patent, Avadel filed a statement under 21 U.S.C. § 355(b)(2)(B) because the patent was listed as claiming a method of use and Avadel was not seeking approval for the REMS system to which that patent’s claims were directed.

Jazz sued Avadel asserting seven patents, of which the REMS patent was the only Orange-Book-listed patent. Avadel asserted a counterclaim requesting that the district court order Jazz to delist the REMS patent from the Orange Book. The district court subsequently held a Markman hearing finding that the REMS patent’s claims were directed to a system and not a method. The district court granted Avadel’s motion for judgment on the pleadings, finding that the REMS patent did not claim “the drug for which the application was approved” and thus had to be delisted from the Orange Book. Jazz appealed.

Jazz argued that because the FDA permitted the REMS patent to be Orange Book listed, Avadel was prohibited from availing itself of the statutory delisting provision. The Federal Circuit disagreed, concluding that the language of the delisting provision was only concerned with whether a listed patent met the provisions’ conditions at the time of the triggering litigation.

Jazz also argued that there was no evidence that Congress imported patent-law [...]

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FDCA’s Exclusive Enforcement Provision Reigns Supreme over State Laws

In its first occasion to interpret § 353b of the Federal Food, Drug, and Cosmetic Act (FDCA), the US Court of Appeals for the Ninth Circuit relied on the “implied preemption doctrine” to affirm a district court’s case dismissal for failure to state a claim under Fed. R. Civ. P. 12(b)(6). Nexus Pharmaceuticals, Inc. v. Central Admixture Pharmacy Services, Inc., Case No. 20-56227 (9th Cir. Sept. 13, 2022) (Kleinfeld, Nelson, VanDyke, JJ.)

Nexus developed and trademarked Emerphed, a US Food & Drug Administration (FDA) approved ready-to-use ephedrine sulfate in a vial. Central Admixture operates a network of compounding pharmacies and sells ephedrine sulfate in ready-to-use syringes without FDA approval, because compounding pharmacies do not need FDA approval. Compounding happens when ingredients in medicines are combined, mixed and altered for individual patients. Under 21 U.S.C. § 353b, drug compounding by “outsourcing facilities” is allowed without FDA approval, but the FDCA excludes compounded drugs that are “essentially a copy of one or more approved drugs.”

The FDCA contains an exclusive enforcement provision prohibiting private enforcement, stating that proceedings to enforce or restrain violations of the FDCA, which includes the compounding statute, must be by and in the name of the United States. To avoid the FDCA’s bar on private enforcement, Nexus alleged that Central Admixture violated the laws of several states in which it sells Emerphed, all of which prohibit the sale of drugs not approved by the FDA. Nexus argued that Central Admixture’s ephedrine sulfate was “essentially a copy” of Emerphed and therefore was excluded from the outsourcing facilities exception. The district court disagreed and dismissed the state law claims under the implied preemption doctrine. The district court explained that all of Nexus’s claims depended on the determination of whether Central Admixture’s ephedrine sulphate was “essentially a copy” of Emerphed, and that the “plain text of the [FDCA] left that determination in the first instance to the FDA and its enforcement process.” Nexus appealed.

The Ninth Circuit explained that the Supremacy Clause of the US Constitution is the “source of preemption doctrine, which invalidates state laws that are contrary to federal statutes,” but noted that there is no clear sorting of case law and no rigid formula to determine when state law runs contrary to federal law. Therefore, the Court relied on several controlling cases regarding the statute governing FDA approval of medical devices, not drugs. Medical device cases are distinguishable because the medical device statute includes an express preemption clause prohibiting states from imposing any safety or effectiveness requirement different from or in addition to those imposed by federal law. In explaining these cases, the Court noted that the claims that were allowed to go forward did not rely on noncompliance with FDA requirements (as Nexus did), but rather on traditional tort law duties. The purported violation of a state law that substantively says “comply with the FDCA” is not a traditional common law tort. The Court also explained that these cases taught that despite a presumption against implied preemption, [...]

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