Ipsen Biopharmaceuticals, Inc. v. Becerra

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IPSEN BIOPHARMACEUTICALS, INC., Plaintiff, v. XAVIER BECERRA, Secretary, United States Department of Health and Human Services, ^[1] et al., Defendants.

No. 20-cv-2437 (DLF)

United States District Court, District of Columbia

September 24, 2021

MEMORANDUM OPINION

DABNEY L. FRIEDRICH, UNITED STATES DISTRICT JUDGE

Before the Court are the plaintiff's Motion for Summary Judgment, Dkt. 11, and the defendants' Cross-Motion for Summary Judgment, Dkt. 16. Because the plaintiff lacks Article III standing, the Court will grant the defendants' motion and deny the plaintiff's motion.

I. BACKGROUND

A. Legal Background

The Food, Drug, and Cosmetic Act (FDCA) prohibits introducing “any new drug” into interstate commerce without prior approval by the Food and Drug Administration (FDA). 21 U.S.C. § 355(a). For this purpose, the Act defines “drugs” to include “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals” and “articles (other than food) intended to affect the structure or any function of the body of man or other animals.” Id. § 321(g)(1)(B)-(C). It further defines “new drug” to mean any drug whose composition “is not generally recognized . . . as safe and effective for use under the conditions prescribed, recommended, or suggested” on its labeling. Id. § 321(p)(1).

There are two paths through which new drugs may obtain FDA approval. First, a company may submit a new drug application (NDA) under § 505 of the FDCA. 21 U.S.C. § 355(b). The FDA may approve the application only if the company demonstrates, often through clinical trials, that its drug is safe and effective for its proposed use. See Id. § 355(d); see also Id. §§ 355(b)(1)(A), (d) (specifying other requirements for NDAs). In the alternative, after the FDA has approved a new drug, and after the exclusivity and patent rights of the drug's sponsor have expired, see Id. § 355(j)(5)(B)(iv), other companies may market generic versions of that drug after the approval of an abbreviated new drug application (ANDA). Id. § 355(j). The FDA may approve an ANDA only upon finding that a generic drug is equivalent to the listed drug in several respects. See id. § 355(j)(4). In particular, the two drugs must share the same active ingredient, conditions of use, route of administration, dosage, and strength. See Id. A generic's sponsor must also show that their product is “bioequivalent” to the listed drug, id. § 355(j)(4)(F), such that “the rate and extent of absorption of the [generic] do not show a significant difference from the rate and extent of absorption of the listed drug … under similar experimental conditions, ” id. § 355(j)(8)(B). Clinical trials are often unnecessary to make these showings. See Pl.'s Br. at 2, Dkt. 11-1. In that respect, the showing required to approve an ANDA is less demanding than that required to approve an NDA.

Different rules apply to the subset of drugs that are also biological products. The Public Health Service Act (PHSA) defines “biological product” to mean “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product . . . applicable to the prevention, treatment, or cure of a disease or condition of human beings.” 42 U.S.C. § 262(i)(1). This definition has changed over time. Although the definition long excluded proteins that were “chemically synthesized polypeptide[s], ” Congress revised it in 2019 to include all proteins, regardless of their origin. Compare Id. § 262(i)(1) (2012) (defining “biological product” to include “protein (except any chemically synthesized polypeptide)”), with Id. § 262(i)(1) (2020) (defining the term to include “protein” without any carveout); Further Consolidated Appropriations Act, 2020, Pub. L. No. 116-94, § 605, 133 Stat. 2534, 3127 (Dec. 20, 2019). The FDA since promulgated a rule to define a “protein” as “any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size.” 21 C.F.R. § 600.3(h)(6).

Just as the FDCA contains two pathways for approving new drugs, the PHSA contains two pathways for approving new biological products. First, a company that seeks to market a new biological product may submit a biological license application (BLA) to the FDA. 42 U.S.C. § 262(a)(1). The agency may approve that application upon finding that the product is “safe, pure, and potent” and that its production facility is “designed to assure” that quality. Id. § 262(a)(C)(i). The PHSA also offers an abbreviated application process: when a company seeks to market a product that is “biosimilar” to or “interchangeable” with a product that has already been approved, it may submit an abbreviated biological license application (ABLA). Id. § 262(k). For this purpose, one product is “biosimilar” to another if it is “highly similar” to that product and if “there are no clinically meaningful differences” between the products “in terms of the safety, purity, and potency.” Id. § 262(i)(2). Likewise, one product is “interchangeable” with another if it is “biosimilar” to that product and if it “can be expected to produce the same clinical result . . . in any given patient.” Id. § 262(k)(4)(A). The FDA may approve an ABLA upon finding sufficient evidence of either biosimilarity or interchangeability. Id. § 262(k)(3).

Whether a new drug qualifies as a biological product has several implications. First, as suggested above, the question determines whether the drug is subject to the general approval regime in § 505 of the FDCA or the more specific regime in the PHSA. See 42 U.S.C. § 262(j) (providing that biological products approved under the PHSA do not also require approval under § 505). The question also determines whether licensing a generic version of the drug requires filing an ANDA or an ABLA-and thus the legal standard the generic must satisfy. Compare 21 U.S.C. § 355(j)(4) (requiring equivalence with the reference drug), with 42 U.S.C. § 262(k)(3) (requiring biosimilarity or interchangeability).

Recognizing the question's effects, Congress has required the FDA to reconsider its classification decisions over time. As relevant here, the Biologics Price Competition and Innovation Act (BPCIA) provides that, beginning on August 23, 2020, any “approved application for a biological product under section 505 of the [FDCA] shall be deemed to be a license for the biological product” under the PHSA. Pub. L. No. 111-148, § 7002(e)(4), 124 Stat. 804, 817 (Mar. 23, 2010). In other words, the Act requires that substances meeting the definition of “biological products” be regulated as biological products, even if the FDA previously approved or regulated them as drugs. Consistent with that Act, the FDA has published a list of biological products that, although approved pursuant to § 505 of the FDCA, it now considers to be licensed under the PHSA. See FDA, List of Approved NDAs for Biological Products That Were Deemed to be BLAs on March 23, 2020, available at https://www.fda.gov/media/119229/download.

B. Factual Background

Plaintiff Ipsen Pharmaceuticals manufactures, markets, and sells a drug called Somatuline Depot. Compl. ¶ 7, Dkt. 1. The drug effects an “extended-release dosing of lanreotide acetate, a synthetic peptide molecule that mimics the naturally occurring hormone somatostatin.” Compl. ¶ 31. The FDA approved the drug in 2007 pursuant to section 505 of the FDCA. Id.; see also A.R. 342-71. The drug is currently licensed “for the treatment of patients suffering from acromegaly, a production of excess growth hormone (GH) by the pituitary gland, to treat adult patients with specific types of tumors in the gastrointestinal tract, and to help ease symptoms caused by carcinoid syndrome.” Compl. ¶ 31.

Although the FDA initially approved Somatuline Depot as a drug, Ipsen argues that the substance also meets the recently-amended definition of “biological product.” Compl. ¶¶ 33-35. More precisely, it argues that Somatuline Depot is a “protein” within the meaning of the PHSA-i.e., an “alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size.” 21 C.F.R. § 600.3(h)(6); see also Compl. ¶ 34 (“Somatuline Depot is[] an amino acid polymer with a specific defined sequence composed of multiple amino acid chains where the total number of amino acids exceeds 40 amino acids.”). For that reason, Ipsen argues that the PHSA requires regulating Somatuline Depot as a “biological product.” Compl. ¶ 46-60.

The FDA disagrees. The agency has not listed Somatuline Depot among the biological products now licensed under the PHSA. Compl. ¶¶ 40-41; see also FDA, List of Approved NDAs for Biological Products That Were Deemed to be BLAs on March 23, 2020, supra. And when Ipsen contacted the agency to argue that Somatuline Depot should be so listed, the agency rejected the company's position. See A.R. 2130-35 (concluding in an internal memo that Somatuline Depot is not a biological product); id. at 2644-58 (reaching the same conclusion in a letter to Ipsen after a telephonic hearing and the review of written submissions). In brief, the FDA reasoned that the proper frame of reference for applying its definition of “protein” is a drug's “active ingredient, ” as opposed to the drug in its entirety. Id. at 2133. Under that view, a drug qualifies as a “protein” only if its active ingredient is an amino acid polymer composed of at least 40 amino acids. See Id. Thus, because lanreotide acetate-the active ingredient of Somatuline Depot-contains only 8 amino acids, the FDA concluded that Somatuline Depot is not a protein. See id.

In this action, Ipsen argues that the FDA's failure to regulate to Somatuline Depot as a biological product...