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Allergan, Inc. v. Crawford

January 19, 2005

ALLERGAN, INC., PLAINTIFF,
v.
LESTER M. CRAWFORD, DVM, PH.D., ACTING COMMISSIONER OF FOOD AND DRUGS, AND TOMMY G. THOMPSON, SECRETARY, HEALTH AND HUMAN SERVICES, DEFENDANTS.



The opinion of the court was delivered by: Rosemary M. Collyer United States District Judge

MEMORANDUM OPINION

This lawsuit arises from a dispute over the Food and Drug Administration's ("FDA") classification of cyclosporine as an "antibiotic" drug. Allergan, Inc. ("Allergan") is a pharmaceutical company that manufactures Restasis(r), a 0.05% topical ophthalmic emulsion of cyclosporine that is used to treat an eye condition known as keratoconjunctivitis or dry eye disease. Allergan argues that cyclosporine is not an "antibiotic" drug because the substance actually suppresses the human body's immune system, making the patient more and not less susceptible to microbial infection. Consistent with its decision in CollaGenex Pharm., Inc. v. Thompson, No. 03- 1405 (D.D.C. January 19, 2005) (" CollaGenex "), the Court finds that the FDA classification decision is supported by the Food and Drug Modernization Act of 1997 ("FDAMA"), Pub. L. No. 105-115, 111 Stat. 2296, and the administrative record. The complaint will be dismissed.*fn1

I. BACKGROUND FACTS

Allergan first contacted FDA about Restasis in December 1998, when it requested a number to submit a New Drug Application ("NDA") for FDA review and approval. FDA's Center for Drug Evaluation and Research ("CDER") assigned number 21-023, which is the number used by Allergan on its NDA request submitted on February 24, 1999. FDA approved the NDA on December 23, 2003. AR Tab 7.*fn2

As described in greater detail below, the Federal Food, Drug, and Cosmetic Act ("FFDCA"), 21 U.S.C. §§ 301-397, as amended, provides patent protection and exclusive marketing for certain drugs. These protections deny FDA the authority to approve a generic version of the drug for the period of three or five years, depending on the degree of innovation reflected in the NDA. The distinction between drugs entitled to market exclusivity/patent protection and those not so entitled, depends on whether the drug is classified as an "antibiotic" that was subject to FDA review prior to 1997. Allergan's NDA requested that Restasis be approved as a non-antibiotic drug, which would protect it from generic competition. See Compl. ¶ 37. However, after approving Restasis, the FDA notified Allergan that Restatis was ineligible for these protections because its active ingredient, cyclosporine, is classified as an "antibiotic." FDA advised Allergan of this determination by telephone and memorialized the decision in a letter to Allergan dated March 3, 2003. AR Tab 8. That letter also assigned Restasis a new NDA number, 50-790, to correspond to its "antibiotic" drug status. Id.

Through a citizen petition submitted to FDA on June 16, 2003, Allergan requested that FDA reclassify cyclosporine as a "non-antibiotic drug" and remove it from the list of drugs that are ineligible for marketing exclusivity and patent listing. AR Tab 9 at 1. On August 1, 2003, Allergan filed a petition for a stay of approval of all generic versions of Restasis until the FDA had ruled on the citizen petition. Allergan instituted this lawsuit on October 31, 2003. On December 18, 2003, FDA denied Allergan's petition.

II. STATUTORY SCHEME

Prior to 1997 and the passage of the FDAMA, "antibiotic" drugs were approved under Section 507 of the FFDCA, 21 U.S.C. § 357 ("Section 507"), and non-antibiotic drugs were approved under Section 505, 21 U.S.C. § 355 ("Section 505"). This difference had a long history, dating back to the development of penicillin, the first drug to have the capacity to kill microbes, i.e., be "anti-biotic." Because penicillin was manufactured in batches through fermentation, its strength and efficacy could vary depending on the rigor of that process.*fn3 Congress required that FDA test all batches of penicillin to ensure that appropriate doses were administered to the military during World War II. Initially, Section 507 applied only to penicillin or any derivative of penicillin; other named antibiotic drugs were added to the statute as they were developed.*fn4 When the FFDCA was amended in 1962, a more generalized definition was added so that the law would not need amending with each new discovery of an antibiotic drug.*fn5

Two key consequences arose from these different treatments. Applicants for generic versions of antibiotic drugs were only requested to show conformance with statutorily-mandated, published standards of identity, strength, quality, and purity for the antibiotic substance, as reflected in antibiotic "monographs" published by FDA. Pharmaceutical companies did not have to submit the safety and efficacy data that was required for pioneer and generic non-antibiotic drugs. Therefore, generic antibiotics were developed and marketed fairly readily. See Glaxo, Inc. v. Heckler, 623 F. Supp. 69, 72 (E.D.N.C. 1985); Abbreviated New Drug Applications, Proposed Rule, 54 Fed. Reg. 28872, 28878 (July 10, 1989). However, antibiotic drugs did not receive the patent listing, patent certification, and marketing exclusivity benefits available to pioneer and nonantibiotic drugs after enactment of the Drug Price Competition and Patent Term Restoration Act ("Hatch-Waxman"), Pub. L. No. 98-417, 98 Stat. 1585 (1984). A. Hatch-Waxman Amendments The significance of the Hatch-Waxman Amendments to FFDCA cannot be understated. Prior to 1984, all applicants seeking to market pioneer drugs or generic non-antibiotic drugs had to file an NDA containing, inter alia, extensive scientific data demonstrating the safety and effectiveness of the drug. See 21 U.S.C. § 355(a)-(b); 21 C.F.R. § 314.50. As a result, few generic non-antibiotic drugs were approved by FDA. See Glaxo, 623 F. Supp. at 72. Hatch- Waxman created an abbreviated approval process for generic non-antibiotic drugs, while retaining incentives for pioneer drugs, such as marketing exclusivity and patent protections. See 21 U.S.C. § 355(jj). The abbreviated new drug application ("ANDA") process shortens the time and effort needed for approval of a generic drug by allowing the applicant to merely demonstrate its product's bioequivalence to the NDA drug, without reproducing the entirety of the NDA's extensive scientific research. See Eli Lilly and Co. v. Medtronic, Inc., 496 U.S. 661, 676 (1990) (describing the ANDA process).

Because Congress still wanted to provide incentives for new drug development, alongside the ANDA process that eased the marketing of generic drugs, Hatch-Waxman entitles an NDA applicant to a period of market exclusivity (3 or 5 years, depending on the degree of innovation reflected in the NDA) which bars FDA approval of a generic ANDA for the NDA product. See 21 U.S.C. § 355 (c)(3)(D)(ii)-(iv), (j)(5)(D)(ii)-(iv). In addition, an NDA applicant must inform FDA about any patent that the NDA applicant claims will protect its exclusivity to market its drug. 21 U.S.C. § 355(b)(1), (c)(2). FDA then publishes patent information for approved drugs in the "Approved Drug Products With Therapeutic Equivalence Evaluations" (the "Orange Book"). See 21 U.S.C. § 355 (b)(1), (c)(2), (j)(7); 21 C.F.R. §314.53(e). Generic drug manufacturers check the Orange Book to determine if a drug product is patent-protected or if it is available for the development of a generic bioequivalent drug.

An ANDA applicant must certify to FDA that (I) patent information has not been filed; (II) the patent has expired; (III) the patent will expire shortly on a date certain; or (IV) the patent is invalid or will not be infringed by the manufacture, use, or sale of the new drug covered by the application. 21 C.F.R. § 355(j)(2)(A)(vii). Under a paragraph IV certification, the applicant must also notify the NDA holder and patent owner concerning its application and its reasoning for applicability of paragraph IV. 21 U.S.C. § 355(b)(2)(B), (j)(2)(B). The filing of a paragraph IV certification "for a drug claimed in a patent or the use of which is claimed in a patent" is an act of infringement. 35 U.S.C. § 271(e)(2)(A). The holder of the patent for the drug may therefore initiate a patent infringement suit upon the ANDA applicant; if it does so, FDA will stay approval of the ANDA application for 30 months, unless a final court opinion is reached earlier, or for the term ordered by the patent court. 21 U.S.C. § 355(c)(3)(C), (j)(5)(B)(iii). It is these protections from early competition for which Allergan sues.

B. FDAMA

When Congress adopted FDAMA in November 1997, it repealed Section 507 of the FFDCA and required that all applications for antibiotic drugs be submitted under Section 505. FDAMA § 125(d)(1) (Transition). In subsection (d)(1), the Transition provided that applications for antibiotic drugs approved under Section 507 before FDAMA would be considered approved under Section 505. Id. However, subsection (d)(2) added the provision that when "the drug that is the subject of the application contains an antibiotic drug and the antibiotic drug was the subject of any application" received by FDA before the enactment of FDAMA, it is exempt from Hatch- Waxman benefits. FDAMA § 125(d)(2); Proposed Rule: Marketing Exclusivity and Patent Provisions for Certain Antibiotic Drugs, 65 Fed. Reg. 3623, 3624-25 (Jan. 24, 2000); Section 507 Repeal Guidance at 2. Specifically, § 125(d)(2) exempts from Hatch-Waxman: any application for marketing in which the drug that is the subject of the application contains an antibiotic drug and the antibiotic drug was the subject of any application for marketing received by the Secretary of Health and Human Services under section 507 of such Act (21 U.S.C. § 357 [Section 507]) before the date of enactment of this Act.

Pub. L. No. 105-115, 111 Stat. 2327 (1997), § 125(d)(2) ( reprinted in 21 U.S.C.A. § 355 Historical and Statutory Notes, "Transition"). Antibiotic drugs that were the subject of pre-FDAMA applications are known as "old antibiotics" and will be so referenced here.

With the enactment of FDAMA in 1997, Congress moved the definition of an "antibiotic" drug to 21 U.S.C.§ 321(jj). The law defines an antibiotic drug as: any drug (except drugs for use in animals other than humans) composed wholly or partly of any kind of penicillin, streptomycin, chlortetracycline, chloramphenicol, bacitracin, or any other drug intended for human use containing any quantity of any chemical substance which is produced by a micro-organism and which has the capacity to inhibit or destroy micro organisms in dilute solution (including a chemically synthesized equivalent of any such substance) or any derivative thereof. 21 U.S.C. § 321(jj).

III. THE ADMINISTRATIVE RECORD

Allergan submitted an NDA to FDA on February 24, 1999, for approval of Restasis (cyclosporine ophthalmic emulsion) Ophthalmic Emulsion, 0.05%, as a non-antibiotic drug under Section 505 of the FFDCA. AR Tab 7. It received approval from FDA dated December 23, 2002, as a non-antibiotic drug. Id. However, on March 3, 2003, FDA sent a second letter to Allergan, in which it noted the repeal of Section 507 by FDAMA and the FDA's listing of the "active drug substances" that were approved before FDAMA, and were therefore affected by the exemption from Hatch-Waxman protections under Section 125(d)(2).*fn6 In this roundabout fashion, FDA informed ...


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