US v. UNDETERMINED QUAN. OF AN ARTICLE OF DRUG, Civ. A. 85-5232.

• Decision Date: 24 August 1987
• Docket Number: No. Civ. A. 85-5232.,Civ. A. 85-5232.
• Citation: 709 F. Supp. 511
• Parties: UNITED STATES of America, Plaintiff, v. UNDETERMINED QUANTITIES OF AN ARTICLE OF DRUG, ... (ANUCORT HC SUPPOSITORIES), Defendants.
• Court: U.S. District Court — District of New Jersey

709 F. Supp. 511

UNITED STATES of America, Plaintiff, v. UNDETERMINED QUANTITIES OF AN ARTICLE OF DRUG, ... (ANUCORT HC SUPPOSITORIES), Defendants.

No. Civ. A. 85-5232.

United States District Court, D. New Jersey.

August 24, 1987.

Paul J. Dillon, Asst. U.S. Atty., Office of the U.S. Attorney, D.N.J., Newark, N.J., David G. Adams, Associate Chief Counsel for Enforcement, U.S. Food and Drug Admin., Rockville, Md., for plaintiff.

Ravin, Sarasohn, Cook, Baumgarten, Fisch & Baime, Peter R. Sarasohn, Rose-land, N.J., Kleinfeld, Kaplan and Becker, Richard S. Morey, Washington, D.C., for claimant G & W Laboratories, Inc.

OPINION

SAROKIN, District Judge.

In this action for seizure and condemnation of a drug, the United States moves for summary judgment.

BACKGROUND

"Anucort Hemorrhoidal Suppositories with Hydrocortisone Acetate" (Anucort) is a prescription drug sold to the public for use in treatment of hemorrhoids. G & W Laboratories, claimant herein, began marketing a drug under this label in 1980.

On November 7, 1985, the United States seized an undetermined quantity of Anucort, pursuant to a complaint of forfeiture. The government's amended complaint, filed November 14, 1985, seeks condemnation of the seized drug on two grounds. First, the government alleges that Anucort is a new drug, as defined by relevant federal statute, that has not been approved by the Food and Drug Administration (FDA). Second, the government alleges that Anucort is a prescription drug under the statute that has been misbranded.

G & W's answer contains several defenses. First, G & W contends that Anucort is not a new drug and therefore not subject to the required FDA approvals. Second, G & W claims that Anucort is exempted from the new drug approval scheme because it was commercially used and sold prior to the statute's enactment date. Third, G & W contends that the court must remand the matter to the FDA for an initial administrative hearing concerning Anucort's status as a new drug. Fourth, G & W argues that FDA's internal enforcement guidelines preclude this action.

On June 11, 1986, the government moved for summary judgment. The government also moved before the Hon. Ronald J. Hedges, U.S. Magistrate, for a stay of discovery pending resolution of the summary judgment motion. G & W cross-moved for a continuance of the summary judgment motion pending further discovery. On October 16, 1986, Magistrate Hedges granted the government's motion for a stay of discovery and denied G & W's motion for a continuance.

G & W appealed the Magistrate's order to this court. On November 24, 1987, at a hearing on the motion, the parties agreed to proceed with the summary judgment motion solely on the ground that Anucort is a new drug because there exists no substantial evidence supporting its safety and efficacy.¹

On February 17, 1987, the court entered an order that 1) reserved decision on G & W's appeal; 2) stated that plaintiff's summary judgment motion would be directed only to "whether there is a lack of substantial evidence to support a finding that the seized drug is generally recognized as effective as contained in Plaintiff's brief in support of its Motion for Summary Judgment"; 3) stating that the government may rely on only one affidavit, to be submitted, "addressing the existence of relevant studies"; 4) granting G & W the right to submit an opposing affidavit; 5) granting the parties leave to depose the respective affiants.

On February 11, 1987, the government submitted the affidavit of Dr. C. Carnot Evans. G & W moved to disregard statements in the affidavit, arguing that its contents violated the court's order. The court, by order dated April 20, 1987, reserved decision on G & W's motion pending its ruling on plaintiff's summary judgment motion. The court also granted G & W the right to depose Dr. Evans and two FDA employees who conducted the literature searches mentioned in Dr. Evans' affidavit.

G & W chose to depose only Mr. Kenter, one of the FDA employees. On May 26, 1987, the court granted G & W's motion to require the government to provide G & W with citations of studies referred to in notes prepared by Mr. Kenter.

The court now considers plaintiff's motion for summary judgment, as reshaped by this procedural history.

DISCUSSION

I. Substantial evidence

Before the court is the question of "whether there is a lack of substantial evidence to support a finding that the seized drug is generally recognized." Plaintiff, to prevail on its motion for summary judgment, must demonstrate that no genuine issue of material fact exists with respect to this question.

"Substantial evidence," in this context, means

evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.

21 U.S.C. § 355(d).²

At dispute is the nature of the "adequate and well-controlled investigations" required by the above definition. The government contends that § 355(d) requires published studies of the product Anucort itself. G & W contends that studies of other drugs containing the same active ingredient (hydrocortisone acetate) as Anucort constitute substantial evidence under § 355(d).³

The court, in evaluating the validity of the FDA's interpretation of § 355, must follow the analysis set forth by the Supreme Court in Chevron U.S.A. Inc. v. Natural Resources Defense Council, Inc., 467 U.S. 837, 104 S.Ct. 2778, 81 L.Ed.2d 694 (1984). If the statutory provision unambiguously expresses Congress' intent on the precise question at issue, the court and the agency must follow the plain language; however, if the provision is silent or ambiguous as to the relevant issue, the court must defer to the agency's interpretation as long as that interpretation is reasonable. See id. at 842-44, 104 S.Ct. 2781-82; Young v. Community Nutrition Inst., 476 U.S. 974, 106 S.Ct. 2360, 2364, 90 L.Ed.2d 959 (1986) (applying Chevron to an FDA interpretation of the Food, Drug, and Cosmetic Act).

Section 355(d), defining "substantial evidence," does not directly address whether the necessary studies must be of the drug product itself. The language employed — "... investigations ... on the basis of which it could be fairly and reasonably be concluded by such experts that the drug will be effective" — is consistent with either party's interpretation. Under such circumstances, Chevron dictates that this court accept FDA's interpretation of § 355(d).

Furthermore, such a result is consistent with prior judicial interpretation of the new drug provisions of the Act.

As an initial matter, "drug," as used in § 321(p) and § 355(d), refers to the product itself, and not simply the product's active ingredients. See United States v. Generix Drug Corp., 460 U.S. 453, 456-57, 103 S.Ct. 1298, 1300-01, 75 L.Ed.2d 198 (1983). Two drugs with the same active ingredients, but different inactive ingredients (excipients), may be released into the body at different rates. See id. at 455, 103 S.Ct. at 1299; Premo Pharmaceutical Laboratories, Inc. v. United States, 629 F.2d 795, 805 (2d Cir.1980). For that reason, courts have rejected arguments that studies of approved drugs containing the same active ingredients as a newly marketed product, in and of themselves, constitute substantial evidence that the new product is generally recognized as safe and effective. See, e.g., United States v. Undetermined Quantities of Various Articles of Drug, 675 F.2d 994, 1001-02 (8th Cir. 1982); Premo Pharmaceutical Laboratories, Inc., 629 F.2d at 805; United States v. Premo Pharmaceutical Laboratories, Inc., 511 F.Supp. 958, 965-973 (D.N.J.1981); Pharmadyne Laboratories, Inc. v. Kennedy, 466 F.Supp. 100, 102-03 (D.N.J.1979), aff'd, 596 F.2d 568, 570 (3d Cir.1979).⁴

However, courts have recognized that studies of a "bioequivalent" drug may be used to show safety and effectiveness of a new product. See United States v. Undetermined Quantities of Various Articles of Drug, 675 F.2d 994, 1001-02 (8th Cir. 1982); United States v. Premo Pharmaceutical Laboratories, 511 F.Supp. at 985-88; cf. United States v. Generix Drug Corp., 460 U.S. at 461, 103 S.Ct. at 1302 (not reaching the question of whether two "demonstrably bioequivalent products" might be considered the same "drug"). Bioequivalent drugs have similar "bioavailability," meaning that the active ingredients in the drugs are absorbed from the drug product at a similar rate and to a similar extent. See 21 C.F.R. § 320.1(a), (e).

Moreover, a 1984 amendment to the Act introducing a scheme for abbreviated new drug applications (ANDAs) verifies the significance of bioequivalence. 21 U.S.C. § 355(j). Such applications permit approval of new drug products that are closely related to previously approved products. An ANDA will be approved only if it contains "information to show that the new drug is bioequivalent to the previously approved drug." 21 U.S.C. § 355(j)(2)(A)(iv). Congress, by establishing an ANDA procedure with a bioequivalence requirement, confirmed that substantial evidence regarding a new product cannot consist merely of studies of a previously approved product containing the same active ingredients.

Neither Congress nor the courts have determined the precise manner by which bioequivalence of two drugs may be established. The government contends first that the Food and Drug Administration (FDA) is the only body capable of properly testing for bioequivalence. See United States v. Premo Pharmaceutical Corp., 511 F.Supp. at 987. Alternatively, the government argues that substantial evidence of bioequivalence must meet the basic statutory definition...