mixture of valproic acid and sodium valproate; and is not a salt; and specifically not a salt of valproic acid." Second Supplement, A.R. at 116; see Lambert Affidavit; Byrn Affidavit. The Wood affidavit simply offered an opinion that divalproex sodium is a salt of valproic acid. The opinion was based on conventions of nomenclature well-known to Abbott's experts.
Neither fairness nor the needs of the reviewing Court required that Abbott be allowed to submit further opinion to which the FDA would inevitably desire to respond. Because the Agency did not abrogate procedural requirements, de novo review by the Court would be inappropriate. See Environmental Defense Fund, Inc. v. Costle, 211 U.S. App. D.C. 313, 657 F.2d 275, 284-85 (D.C. Cir. 1981). Similarly, remand to the Agency is not required unless the Court finds that the factual finding -- that divalproex sodium is a salt of valproic acid -- was "arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law." 5 U.S.C. § 706(2)(A); see Citizens to Preserve Overton Park v. Volpe, 401 U.S. 402, 414, 28 L. Ed. 2d 136, 91 S. Ct. 814 (1971) (judicial review of informal rulemaking is conducted under section 706(2)(A)).
B. The FDA's Finding That Divalproex Sodium Is A Salt Of Valproic Acid Was Not Arbitrary And Capricious
While the parties agree in principle that judicial review in this case must be conducted under the "arbitrary and capricious" standard, their elaboration of that standard varies markedly. It is well-settled, however, that "the scope of review . . . is narrow and a court is not to substitute its judgment for that of the agency. . . . The agency must examine the relevant data and articulate a satisfactory explanation for its action including a 'rational connection between the facts found and the choice made.'" Motor Vehicle Manufacturers Association v. State Farm Mutual Automobile Insurance Co., 463 U.S. 29, 43, 77 L. Ed. 2d 443, 103 S. Ct. 2856 (1983); see Eagle-Picher Industries v. E.P.A., 759 F.2d 905, 921 (D.C. Cir. 1985). Much deference is accorded the agency, and its action is presumed to be valid. See United Transportation Union v. Lewis, 228 U. S. App. D.C. 447, 711 F.2d 233, 252 (D.C. Cir. 1983) (citing Overton Park, 401 U.S. at 415). Deference is particularly advised when the administrative action is based on the expertise of the agency. See Baltimore Gas and Electric Co. v. Natural Resources Defense Council, Inc., 462 U.S. 87, 103, 76 L. Ed. 2d 437, 103 S. Ct. 2246 (1983); Community Nutrition Institute v. Young, 249 U.S. App. D.C. 150, 773 F.2d 1356, 1363 (D.C. Cir. 1985) ("court will not substitute its judgment on highly technical and factual matters for that of the [FDA which is] charged with the supervision of the industry"). Nevertheless, the Court's inquiry into the administrative record must be "'searching and careful' . . . to ensure that the agency's decision was a product of reasoned decisionmaking based upon a consideration of relevant factors." Motor Vehicle Manufacturers Association v. E.P.A., 247 U.S. App. D.C. 268, 768 F.2d 385, 389 n.6 (D.C. Cir. 1985) (citing Small Refiner Lead Phase-Down Task Force v. E.P.A., 227 U.S. App. D.C. 201, 705 F.2d 506, 520 (D.C. Cir. 1983)).
The FDA's determination that divalproex sodium is a salt of valproic acid falls well within the bounds of reasoned decisionmaking. The Agency was presented with authoritative but conflicting opinions regarding the appropriate basis for classification of salts. After considering the distinctions drawn by Abbott's experts, the FDA reasonably concluded that classification should be based on known standards of nomenclature. At the same time, it noted that Abbott's attempt to exclude divalproex sodium from classification as a salt was based on physical properties of the drug that are irrelevant to classification. Agency Decision at 6, A.R. at 197. Further, the Agency reasonably declined to adopt Abbott's method for classifying salts because it was not based on any definition of salt but a weighing of the similarities of a drug to "typical salts." Id. Such a method would be far less predictable and manageable than the nomenclature method. Accordingly, the Court declines to second-guess the scientific expertise of the FDA and concludes that the Agency's classification of divalproex sodium as a salt was not arbitrary or capricious.
C. The FDA's Definition Of "Active Ingredient" As Used In Section 355(j)(4) Of The Hatch-Waxman Amendments
Essential to application of the marketing exclusivity provisions of the Hatch-Waxman Amendments is the definition of the term "active ingredient." Abbott argues that the term refers to the ingredient as it exists in the final dosage form of the product; that is, the form the product takes prior to ingestion by the patient. Letter from Bryan Yolles, Counsel for Abbott Laboratories, to Ann Witt, Food and Drug Administration (Feb. 27, 1987), reproduced in A.R. at 139A-F. Conversely, the FDA has stated that it believes the term applies to the pharmaceutically active ingredient (active moiety) of the drug.
In this case, the dispute is whether the active ingredient is divalproex sodium -- the ingredient that appears in the final dosage form of depakote -- or valproic acid -- the chemical that yields the therapeutic effect. The disagreement is material to application of the marketing exclusivity provisions of the Amendments. As the discussion below explains, Abbott's definition leads to irreconcilable results while the FDA's definition is inconsistent with a definition assigned to the same term as used in section 355(j)(2).
The marketing exclusivity provisions at issue in this case are an element of a coordinated legislative effort to streamline administrative procedures for the approval of generic drugs. See Mead Johnson, 838 F.2d at 1333; H.R. REP. NO. 98-857 at 14-15, 1984 U.S.CODE. CONG. & ADMIN. NEWS at 2647-48. To qualify for the abbreviated new drug application process, a drug must have the same active ingredients as the drug of which it is a copy. 21 U.S.C. §§ 355(j)(2)(A)(ii) & (j)(2)(A)(iii). On several occasions, the FDA has determined a drug to be ineligible for the ANDA process because this requirement was not satisfied. In making this determination, the Agency has stated that "the term active ingredient in the Act refers to the active ingredient found in the final dosage form prior to the administration of [the] product to the patient, rather than to any resultant form the drug may take following administration." Letter from Dr. Peter H. Rheinstein, Center for Drugs and Biologics, to I.R. Berry, Pharmacaps, Inc. (Feb. 13, 1986) (emphasis added), reproduced in A.R. at 30; Letter from Dr. Peter H. Rheinstein to George W. Severn, Rowell Laboratories, Inc. (June 5, 1986), reproduced in A.R. at 36. Abbott asserts that the same definition should apply to the term as used in sections 355(j)(4)(D)(i)-(v). The FDA disagrees.
In its decision denying Abbott's citizen petition, the FDA stated:
Abbott's interpretation is [not] consistent with Congressional intent, nor is it mandated by FDA's interpretation of "same active ingredient" for purposes of permitting the marketing of new drug products through abbreviated applications. This interpretation of "same active ingredient" is inapplicable to the agency's determination of the period of exclusivity for which Depakote qualifies, on two independent grounds. First, as already explained, Depakote is a salt of an already approved active ingredient and thus does not fall within the plain language of eligibility for the exclusivity provisions at issue. Second, neither the language of, nor the policies underlying, the exclusivity provisions are the same as those of the ANDA eligibility provisions in section 505(j)(2)(C).
Agency Decision at 14-15, A.R. at 205-06. The first of the Agency's "grounds" for adopting an inconsistent definition of "active ingredient" defies understanding. At best, the explanation simply begs one of the legal issues about which the parties disagree. The second ground recites fundamental principles of statutory interpretation.
Because definition of "active ingredient" demands interpretation of the Hatch-Waxman Amendments, the first question is "whether Congress has directly spoken to the precise question at issue." Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837, 842, 81 L. Ed. 2d 694, 104 S. Ct. 2778 (1984).
If the intent of Congress is clear, that is the end of the matter; for the court, as well as the agency, must give effect to the unambiguously expressed intent of Congress. If, however, the court determines that Congress has not directly addressed the precise question at issue, the court does not simply impose its own construction on the statute, as would be necessary in the absence of an administrative interpretation. Rather, if the statute is silent or ambiguous with respect to the specific issue, the question for the court is whether the agency's answer is based on a permissible construction of the statute.
Id. at 842-43 (footnotes omitted). As with the arbitrary and capricious standard, deference to the agency is appropriate, and "the agency's construction is adequate if it falls within the permissible range of interpretations." Office of Consumers' Counsel v. F.E.R.C., 251 U.S. App. D.C. 208, 783 F.2d 206, 218 (D.C.Cir.1986).
Following Chevron U.S.A., the Court notes that neither the Amendments nor the legislative history reveals any congressional desire to imbue with contradictory meaning the term "active ingredient" as used in the abbreviated new drug application, 21 U.S.C. § 355(j)(2)(A), and exclusive marketing provisions, id. § 355(j)(4)(D), of the Amendments. Thus, in the context of this case, the inquiry is whether the FDA reasonably offers contradictory definitions of "active ingredient" for two subsections of the same section of the Hatch-Waxman Amendments. The Agency argues that the contradictory definitions are necessary to fulfill the distinct purposes of the two subsections. As used in the ANDA subsection, "active ingredient" must be construed narrowly to ensure that the abbreviated approval procedures are not applied to drugs that are not truly the same as previously approved drugs. With respect to the exclusive marketing subsection, however, the Agency perceives a congressional intent to define broadly the term "active ingredient" in order to restrict the exclusive marketing privilege to those drugs that are genuinely new chemical entities.
Although the FDA may state a logical policy for the application of the subsections at issue, that policy is entirely an invention of the Agency. Moreover, it does not reflect a judgment based on the expertise of the Agency; instead, it is a uniquely legislative evaluation of the benefit of increased availability of generic drugs and the need for continued research for the development of pioneer drugs. Both subsections are part of a coordinated scheme designed to foster these competing interests. Rather than being different, their purposes are complementary. In the absence of an express congressional statement or other evidence of congressional purpose, the Agency's diametrically conflicting interpretations of "active ingredient" cannot be accepted. See Barnson v. U.S., 816 F.2d 549, 554 (10th Cir.1987); Firestone v. Howerton, 671 F.2d 317, 320 (9th Cir.1982); cf. Laffey v. Northwest Airlines, Inc., 185 U.S. App. D.C. 322, 567 F.2d 429, 461, n. 230 (D.C.Cir.1976) (same term in civil and criminal sections given different meaning because civil section had no punitive purpose). Such statutory construction simply is unreasonable.
Given this disposition of the FDA's conflicting definitions of "active ingredient," the question necessarily arises whether the definition espoused in the Agency's ANDA opinions will prevail or the broader definition proffered in this case will be adopted. Although the Court cannot be certain which the FDA will prefer, the choice is irrelevant in this case.
D. Regardless Of The Definition Of Active Ingredient, Depakote Is Entitled To Two Years Of Marketing Exclusivity
With the several peripheral and threshold issues resolved, the Court turns to the focus of the parties' arguments-the exclusive marketing provisions. Simply stated, the question is whether subsection (i) or subsection (v) of 21 U.S.C. § 355(j)(4)(D) applies to Abbott's product Depakote. Subsection (i) provides:
If an application (other than an abbreviated new drug application) submitted under subsection (b) for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (b), was approved during the period beginning January 1, 1982, and ending on the date of the date of enactment of this subsection [September 24, 1984], the Secretary may not make the approval of an application submitted under this subsection which refers to the drug for which the subsection (b) application was submitted effective before the expiration of ten years from the date of the approval of the application under subsection (b)
Recast in comprehensible language, this subsection provides that a drug that was approved between January 1, 1982 and September 24, 1984 by the FDA pursuant to the complete new drug application procedure is entitled to ten years of protection from competition by generic copies if neither the active ingredient of that drug, the salt of the active ingredient, nor the ester of the active ingredient had previously been approved by the FDA. Abbott asserts that its new drug Depakote has divalproex sodium as its active ingredient and that neither this ingredient, a salt of it, nor an ester of it had previously been approved by the FDA.
The FDA contends that the active ingredient in Depakote is valproic acid. As Abbott admits, valproic acid is the active ingredient in Depakene which was approved by the FDA approximately two years before Depakote. If the Agency is correct, subsection (i) does not apply to Depakote, and Abbott is not entitled to ten years of exclusive marketing of Depakote.
The other subsection of the exclusive marketing provisions that is implicated by the parties' dispute is subsection (v) which states:
If an application (or supplement to an application) submitted under subsection (b) for a drug, which includes an active ingredient (including any ester or salt of the active ingredient) that has been approved in another application under subsection (b), was approved the period beginning January 1, 1982, and ending on the date of the enactment of this subsection [September 24, 1984], the Secretary may not make the approval of an application submitted under this subsection which refers to the drug for which the subsection (b) application was submitted . . . before the expiration of two years from the date of enactment of this subsection [September 24, 1984].