Amarin Pharm. Ir. Ltd. v. Food & Drug Admin.

• Decision Date: 28 May 2015
• Docket Number: Civil Action No. 14–cv–00324 (RDM)
• Citation: 106 F.Supp.3d 196
• Parties: Amarin Pharmaceuticals Ireland Limited, Plaintiff, v. Food and Drug Administration, Margaret A. Hamburg, M.D., Commissioner of Food and Drugs, and Kathleen Sebelius, Secretary of Health and Human Services, Defendants.
• Court: U.S. District Court — District of Columbia

106 F.Supp.3d 196

Amarin Pharmaceuticals Ireland Limited, Plaintiff,

v.Food and Drug Administration, Margaret A. Hamburg, M.D., Commissioner of Food and Drugs, and Kathleen Sebelius, Secretary of Health and Human Services, Defendants.

Civil Action No. 14–cv–00324 (RDM)

United States District Court, District of Columbia.

Signed May 28, 2015

Christopher N. Sipes, Benjamin C. Block, Bradley K. Ervin, Covington & Burling LLP, Matthew Joseph Berns, U.S. Department of Justice, Washington, DC, for Plaintiff.

Ann Frances Entwistle, Gerald Cooper Kell, Andrew E. Clark, Cindy Jane Cho, U.S. Department of Justice, Washington, DC, for Defendants.

MEMORANDUM OPINION

RANDOLPH D. MOSS, United States District Judge

Amarin Pharmaceuticals Ireland Limited ("Amarin") challenges the Food and Drug Administration's determination that Amarin's new drug, Vascepa (icosapent ethyl) Capsules ("Vascepa"), is not entitled to a five-year period of market exclusivity under the Federal Food, Drug, and Cosmetic Act ("FDCA"). That period of exclusivity is available for a new drug, if "no active ingredient (including any ester or salt of the active ingredient)" of the drug "has been approved in any other application" for new drug approval. Here, the Food and Drug Administration ("FDA" or "Agency") denied five-year market exclusivity for Vascepa because Vascepa's active ingredient—a single molecule—is one component of a mixture that makes up the "active ingredient" of a previously approved drug. For the reasons set forth below, the Court concludes that the FDA's decision must be set aside, and the matter is remanded to the Agency for further proceedings consistent with this decision.

I. BACKGROUND

A. Statutory and Regulatory Background

1. The Hatch–Waxman Amendments

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98–417, 98 Stat. 1585 (1984). Popularly known as the "Hatch–Waxman Amendments," the Act sought to balance two competing policy goals: (1) encouraging the development of generic drugs to increase competition and lower prices in the pharmaceutical industry, while (2) maintaining incentives for pharmaceutical companies to invest in innovation and the creation of new drugs. Facing this "classic question of the appropriate trade-off between greater incentives for the invention of new products and greater affordability of those products," Abbott Labs. v. Young, 920 F.2d 984, 985 (D.C.Cir.1990), Congress struck a compromise. It established an expedited process for obtaining approval for generic drugs, but, at the same time, it provided increased intellectual property rights and periods of market exclusivity for those pioneer manufacturers that invent new drugs.

The two sides of the compromise are codified in separate aspects of the Hatch–Waxman Amendments. On the one hand, to streamline the process for bringing new generic drugs to market, Congress created the "abbreviated new drug application" ("ANDA") process, under which a manufacturer can obtain FDA approval for a generic drug by demonstrating that it has the same "active ingredient" or "active ingredients" as a drug previously approved as safe and effective and that the generic drug is otherwise equivalent to that drug. See 21 U.S.C. § 355(j)(2)(A). This significantly reduces the time and expense required to obtain approval for generic drugs; previously, in order to obtain approval in most cases, manufacturers were required to submit a full "new drug application" ("NDA") with clinical data sufficient to demonstrate the drug's safety and effectiveness, even where the drug was merely a generic version of a previously approved drug.

On the other hand, in order to maintain incentives for pioneer drug manufacturers to research and invest in new drugs, Congress provided that most drugs with new "active ingredients" would be entitled to a five-year period of marketing exclusivity. Specifically, Congress provided a five-year period of exclusivity for approved new drugs, "no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application." 21 U.S.C. §§ 355(c)(3)(E)(ii), 355(j)(5)(F)(ii). Esters and salts are molecules that form in chemical reactions when the hydrogen atom of an acid molecule is replaced by another substance.¹ Esters and salts are typically closely related to their parent acid molecules.

Congress also provided a more limited three-year period of exclusivity for new drugs that contain "an active ingredient (including any ester or salt of the active ingredient) that has been approved in another application" in certain circumstances where the drug's sponsor was required to conduct new research to gain approval. See 21 U.S.C. §§ 355(c)(3)(E)(iii), 355(j)(5)(F)(iii). This three-year exclusivity period applies where, for instance, a previously approved drug is approved to treat a new condition, or where approval is sought for a new salt or ester form of the active ingredient in a previously approved drug. In practice, however, more than two years separates the five- and three-year exclusivity periods, since the five-year exclusivity provision bars the FDA from accepting an application for approval of a competing drug, see 21 U.S.C. §§ 355(c)(3)(E)(ii), 355(j)(5)(F)(ii), while the three-year exclusivity provision merely precludes FDA from approving such an application, 21 U.S.C. §§ 355(c)(3)(E)(iii), 355(j)(5)(F)(iii). Because it often takes considerable time for the FDA to approve an application once it is accepted, the difference in the length of the actual periods of exclusivity under the two provisions can be significantly greater than two years.

2. FDA Regulations And Abbott Labs

Section 314.108 of the FDA's regulations implements the five-year exclusivity provision.See 21 C.F.R. § 314.108. Although the statute refers to a new drug's "active ingredient," the regulations do not directly define that term. Instead, they grant five-year exclusivity to "new chemical entit[ies]." 21 C.F.R. § 314.108(b)(2).² The regulations define a "new chemical entity" (or "NCE") as any "drug that contains no active moiety that has been approved by FDA in any other application submitted under section 505(b)." 21 C.F.R. § 314.108(a). "Active moiety," in turn, is defined as "the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance."³ Id. For salts, esters, and noncovalent derivatives, a molecule's "active moiety" can be thought of as its core; salt, ester and noncovalent derivative versions of the same basic molecule have different appendages, but they share the same active moiety. In other words, the FDA interpreted the statutory requirement that five-year exclusivity be granted to drugs no "active ingredient (including any ester or salt of the active ingredient) of which has been approved" to provide five-year exclusivity only to drugs that contain no active moiety that has been approved in a prior application.

The regulatory history makes clear that the Agency adopted the "active moiety" approach to address an issue that is not implicated in this case: the availability of exclusivity for multiple closely related forms of the same basic molecule. By defining "active moiety" to mean "the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt, ... or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule," 21 C.F.R. § 314.108(a) (emphasis added), the FDA was able to withhold exclusivity not only from esters or salts of a previously approved molecule, but also from other derivative molecules that it concludes are insufficiently innovative to merit five-year exclusivity.

When the FDA first proposed regulations implementing this "active moiety" approach in 1989, it explained that the approach was justified because, in its view, Congress "did not intend to confer significant periods of exclusivity on minor variations of previously approved chemical compounds." See Abbreviated New Drug Application Regulations, 54 Fed. Reg. 28,872, 28,898 (proposed July 10, 1989). Almost a year and a half after the FDA issued those proposed regulations, the Court of Appeals addressed the FDA's interpretation of the statutory exclusivity provision in Abbott Laboratories v. Young, 920 F.2d 984 (D.C.Cir.1990) (" Abbott Labs "). In that case, the FDA argued that it could treat all forms of a molecule that eventually produce the same "active moiety" alike for purposes of exclusivity.⁴ See id. at 988. The Agency sought to tether this authority to the statutory text by construing the term "including" broadly, and arguing that the parenthetical phrase "(including any ester or salt of the active ingredient)" was "merely illustrative." Id. With the statute so construed, the FDA argued that it was permitted to treat other forms of an active ingredient in the same manner as "esters" and "salts." See id. ; Abbreviated New Drug Application Regulations; Patent And Exclusivity Provisions, 59 Fed. Reg. 50,338, 50,358 (final rule) (explaining that in Abbott Labs, the FDA interpreted the term "active ingredient" "narrowly to refer to the form of the moiety in the product, but interpreted the parenthetical phrase ‘(including any salt or ester of the active ingredient)’ broadly to include all active ingredients that are different but contain the same active moiety."). The Court of Appeals rejected that interpretation of the exclusivity provision as "linguistically infeasible." Abbott Labs, 920 F.2d at 988.

The FDA did not retreat from its "active moiety" approach. Instead, in 1994 it promulgated the final regulations discussed above, under which five-year exclusivity is available only for ...