The opinion of the court was delivered by: Emmet G. Sullivan United States District Judge
Plaintiff, Barr Laboratories, Inc. ("Barr Labs" or "Barr"), commenced this action against the Secretary of Health and Human Services (Tommy Thompson), the Deputy Commissioner of Food and Drugs (Lester Crawford), and the U.S. Food and Drug Administration ("FDA")to enjoin the FDA from refusing to recognize plaintiff's Abbreviated New Drug Application ("ANDA") as finally approved on April 1, 1987, and as effective on August 20, 2002. In addition, plaintiff seeks to enjoin the agency from taking any action to prevent Barr from immediately marketing a generic 10 mg tamoxifen citrate product ("tamoxifen") under Barr's ANDA No. 70-929. AstraZeneca Pharmaceuticals ("Astra") intervened on behalf of federal defendants.
Without objection from the parties, the Court consolidated plaintiff's request for injunctive relief with the proceedings on the merits in accordance with Fed. R.Civ.P.65(a)(2). Pending before the Court are cross-motions for summary judgment pursuant to Fed.R.Civ.P. 56. Upon consideration of the parties' motions, oppositions, replies and oral arguments, as well as the statutory and case law governing the issues, and for the following reasons, the Court concludes that defendants' and intervenor's motions for summary judgment are GRANTED and plaintiff's motion for summary judgment is DENIED.
Essentially, the Court is required to consider the legal effect of a letter issued by the FDA on April 1, 1987. Plaintiff alleges that the letter contained a "final approval" of its application to market a generic version of the breast cancer drug tamoxifen citrate on August 20, 2002. It claims that the FDA violated the Federal Food, Drug and Cosmetic Act ("FDCA") and acted arbitrarily, capriciously and in a manner otherwise contrary to law under the Administrative Procedure Act ("APA") by "converting" the FDA's 1987 final approval of its Abbreviated New Drug Application into a "tentative" approval and preventing the marketing of its 10mg tamoxifen citrate tablets before expiration of AstraZeneca's newly acquired pedriatic exclusivity. Thus, plaintiff challenges the validity of the FDA's decision to award to Astra a six-month pediatric exclusivity extension for tamoxifen.
Defendants contend that plaintiff never received "final" approval of its application to market tamoxifen and that such approval cannot become effective until the conclusion of Astra's pediatric exclusivity provision. According to defendants, the effective date of approval for each generic applicant was subject to a period of delay pending the expiration of Astra's patent protection. They maintain that, as of the date Astra received its six-month pediatric extension, no generic applicant's approval had gone into effect. Semantic differences aside, defendants claim, plaintiff is on identical legal and equitable footing as its generic competitors, who must wait until the expiration of Astra's pediatric exclusivity before marketing their products.
I. Abbreviated New Drug Approval
Prior to 1984, FDA approval of a new drug application was granted without reference to intellectual property rights or interests. Congress recognized that periods of market exclusivity would provide valuable incentives for drug manufacturers to engage in the research and development of new drugs. See H.R. Rep. No. 98-857, Pt. I, 98th Cong., 2d Sess. at 15, reprinted in 1984 U.S.C.C.A.N. 2647, 2648. Moreover, the legislators understood that the goal of encouraging innovation had to be balanced against that of promoting competition. See id. at 14. With the objective of addressing both concerns, Congress passed the Drug Price Competition and Patent Term Restoration Act, generally known as the Hatch-Waxman Amendments, in 1984. *fn1 The Hatch-Waxman Amendments created a system for FDA review and approval of applications to market generic versions of previously approved drugs. Specifically, Hatch-Waxman eliminated the requirement that companies seeking to market a generic drug duplicate human clinical tests and established, in its place, the "ANDA" process.
Under the Federal Food, Drug and Cosmetic Act, a company seeking to market a drug that has never been approved in the United States must submit a New Drug Application ("NDA") to the FDA. Under the Hatch-Waxman Amendments, a company may obtain FDA approval to market a generic version of a previously approved drug by submitting an ANDA demonstrating, inter alia, that the generic version of the drug is the same as ("bioequivalent" to) the NDA-approved version of the drug. *fn2
The FDCA requires an ANDA applicant seeking approval of a generic drug to reference the specific listed drug that it intends to duplicate. See 21 U.S.C. § 355(j)(2)(A). "Listed drugs" are new drug products that have been approved under the FDCA for safety and effectiveness and that have not been withdrawn from sale for reasons of safety and effectiveness. See 21 C.F.R. § 314.3(b). A "drug product" is a finished dosage form that contains a drug substance generally in association with one or more ingredients. See id. A "drug product" is an "active ingredient that is intended to furnish pharmacological activity or other direct effect . . . but does not include intermediates used in the synthesis of such ingredient." Id.
The ANDA applicant must also submit information to show that "the route of administration, the dosage form, and the strength of the new drug are the same as those of the listed drug." See 21 U.S.C. §355(j)(2)(iii). The FDA has concluded that each strength of a drug product is a separately listed drug. See, e.g., Apotex, Inc. v. Shalala, 53 F. Supp. 2d 454, 456 (D.D.C. 1999), aff'd, 1999 WL 956686 (D.C. Cir. 1999).
Under the FDCA, an ANDA must also contain a "certification" with respect to each patent that claims the pioneer drug or the method of the drug's use. See 21 U.S.C. § 355(j)(2)(A)(vii). The certification must state one of the following:
(I) that the required patent information relating to such patent has not been filed;
(II) that such patent has expired;
(III) that the patent will expire on a particular date;
(IV) that such patent is invalid or will not be infringed upon by the drug for which approval is being sought.
If certification is made under paragraphs I or II indicating that patent information pertaining to the drug or its use has not been filed with the FDA or that the patent has expired, approval of the ANDA may be made effective immediately. See 21 U.S.C § 355(j)(5)(B)(i). A certification pursuant to 21 U.S.C. § 355(j)(2)(A)(vii)(III), or a "paragraph III certification," certifies that the ANDA applicant seeks approval to market a product after expiration of the patents listed in the Orange Book. *fn3 A paragraph IV certification requires that the ANDA applicant give notice of the filing of the ANDA to the patent owner and the ANDA holder for the listed drug. The notice must include a detailed statement of the legal and factual bases for the applicant's opinion that the patent is either invalid or will not be infringed. See 21 U.S.C. § 355(j)(2)(B); 21 C.F.R. § 314.95. The FDA may approve an ANDA with a paragraph IV certification, and the approval may become effective immediately, despite the unexpired patent, unless an action for patent infringement is brought against the ANDA applicant within 45 days of the date on which the patent owner and the NDA holder receive notice of the paragraph IV certification. See 21 U.S.C. § 355(j)(5)(B)(iii); 21 C.F.R. § 314.107(f)(2). If a patent action is brought within 45 days of the notice, approval of the ANDA will not become effective until at least 30 months from the date of receipt of notice unless a final decision is reached earlier in the patent case or the patent court mandates a longer or shorter period. See 21 U.S.C. § 355(j)(5)(B)(iii).
II. Pediatric Exclusivity Provision
In 1997, Congress amended the FDCA in order to provide economic incentives for drug manufacturers to conduct pediatric studies of drugs. The so-called "pediatric exclusivity" provision, 21 U.S.C. § 355(a), rewards drug manufacturers with a six-month extension of pre-existing market protection in return for conducting pediatric studies at the FDA's request. If the FDA makes a request and the NDA holder satisfies that request's requirements, pediatric exclusivity provides for a six-month delay in the effective date of pending ANDAs. See 21 U.S.C. § 355a(c)(2)(A). When pediatric exclusivity is awarded, the statute attaches six months to any exclusivity or patent protection already in place for the drug in question.
Following the passage of the Hatch-Waxman Amendments in 1984, Congress directed the FDA to promulgate necessary regulations through notice and comment rulemaking under the APA. See Pub. L. No. 98-417, 98 Stat. 1585, at § 105(a)(1984). Until such time as the FDA adopted final regulations, Congress authorized the Agency to review and approve ANDAs under its then-existing regulations. Id.
In 1985, the FDA's regulations provided that the "date of the agency's approval letter is the date of approval of the application." 21 C.F.R. § 314.105(a)(1985). The text of the provision remained unchanged in 1987. 21 C.F.R. § 314.105(a)(1987).
AstraZeneca holds the New Drug Application for tamoxifen citrate and sells the product under the brand name of Novaldex®. An affiliate of Astra holds United States patent No. 4,536,516 (the " '516 patent"). *fn4
On December 19, 1985, plaintiff filed an ANDA seeking FDA approval to market a generic copy of Astra's 10 mg tamoxifen citrate tablet. Plaintiff's ANDA contained a paragraph III certification to Astra's 516' patent under 21 U.S.C. § 355(j)(2)(A)(vii)(III), indicating that plaintiff did not intend to begin marketing the product until the date of Astra's patent expiration.
On April 1, 1987, FDA issued a letter "approv(ing)" Barr Labs' 10 mg. tamoxifen ANDA. The letter stated, in part:
We have completed the review of this abbreviated application and have concluded that the drug is safe and effective for use as recommended in the submitted labeling. Accordingly, the application is approved; however the effective date of approval is delayed until August 20, 2002 pursuant to 21 U.S.C. 355(j)(4)(B) relating to patent rights.
Following receipt of the FDA's letter, plaintiff's tamoxifen product was listed in the agency publication Approved Drug Products with Therapeutic Equivalence Evaluations with an approval date of April 1, 1987 and an effective date of August 20, 2002.
On September 16, 1987, plaintiff changed its paragraph III certification to a paragraph IV certification, indicating its intent to challenge Astra's '516 patent. On November 2, 1987, in response to plaintiff's paragraph IV certification, Astra filed suit against plaintiff, thereby triggering a 30-month stay of approval of plaintiff's Abbreviated New Drug Application. On March 15, 1990, the FDA sent plaintiff a letter indicating that the 30-month stay of approval was due to expire on March 29, 1990 and that the effective date of its ANDA approval had been modified from August 20, 2002 to March 29, 1990. In a letter dated March 20, 1990 plaintiff acknowledged receipt of the FDA's letter modifying the effective date of its ANDA and informed the Agency that its patent litigation was ongoing and would not be resolved prior to the newly established effective date. On March 21, 1990 the FDA received a copy of a March 13, 1990 stipulation by the parties in the patent litigation. The stipulation stated that the 30-month approval stay would be extended until the date of final judgment in the patent case, but for no longer than six months from March 25, 1990.
On July 10, 1989, the FDA proposed regulations to implement Hatch-Waxman. See Abbreviated New Drug Application Regulations, 54 Fed. Reg. 28872 (proposed July 10, 1989). The proposal contained the following suggested regulation:
FDA will approve an abbreviated new drug application and send the applicant an approval letter if none of the reasons . . . for refusing to approve the...application apply. The date of the agency's approval letter is the date of approval of the abbreviated new drug application. A new drug product approved under this paragraph may not be introduced . . . into interstate commerce until approval . . . is effective. Ordinarily, the effective date of approval will be stated in the approval letter.
In June of 1992, FDA's final regulations became effective. See 57 Fed. Reg. 17950 (Apr. 28, 1992) (codified at 21 C.F.R. § 314). In contrast to the 1989 proposed regulations, the final provisions referred to "tentative" ANDA approval:
FDA will approve an abbreviated new drug application and send the applicant an approval letter if none of the reasons in § 314.127 for refusing to approve the abbreviated new drug application apply. The approval becomes effective on the date of the issuance of the agency's approval letter unless the approval letter provides for a delayed effective date. An approval with a delayed effective date is tentative and does not become final until the effective date. A new drug product approved under this paragraph may not be introduced or delivered for introduction into interstate commerce until approval of the abbreviated new drug application is effective. Ordinarily, the effective date of approval will be stated in the approval letter. 57 Fed. Reg. 17950, 17989 (Apr. 28, 1992) (adopted 21 C.F.R. § 314.105(d).
On April 7, 1993, plaintiff informed the FDA that it had settled its patent litigation with Astra. Plaintiff withdrew its paragraph IV certification to the '516 patent as part of the settlement agreement and submitted in its place a new paragraph III certification. This change reset the effective date for plaintiff's marketing of tamoxifen to August 20, 2002, the date corresponding to Astra's patent expiration. As part of the patent litigation settlement, plaintiff and Astra entered into a distribution and supply agreement, whereby plaintiff obtained the right to market Astra's tamoxifen product under its name. Since 1993, therefore, plaintiff has been marketing a "generic" tamoxifen product under its own label.
Since the 1993 settlement, the validity and enforceability of the '516 patent have been upheld twice by federal district courts in two fully litigated cases involving other parties who filed tamoxifen citrate ANDAs. In the case of Zeneca Ltd. v. Novopharm Ltd., 111 F.3d 144 (Fed Cir. 1997), the District Court of Maryland rejected Novopharm's claim of invalidity and the Federal Circuit affirmed. In Zeneca Ltd. v. Pharmachemie B.V., 37 F. Supp. 2d 85 (D. Mass. 1999), the defendant similarly asserted that the '516 patent was invalid and unenforceable. Following a trial, the District of Massachusetts ruled that the '516 patent was valid, enforceable and infringed by Pharmachemie. See Zeneca Ltd. v. Pharmachemie B.V., 37 F. Supp.2d 85 (D. Mass. 1999).
In 1997, Congress passed the Food and Drug Administration Modernization Act ("FDAMA"), which included among its terms pediatric exclusivity provisions. 21 U.S.C. § 355(a).
In a letter to the FDA dated September 4, 1998, plaintiff stated that:
On March 15, 1990, FDA granted tentative approval for Barr's tamoxifen ANDA. Since Barr settled with ICI to avoid the risk of reversal on appeal, Barr cannot obtain final approval until the '516 patent is either defeated or expires. Nevertheless, Barr stands ready and waiting for the first opportunity to obtain final approval and to market its own generic version of tamoxifen. Thus, ...