United States v. Atropine Sulfate 1.0 Mg. (Article of Drug) Dey-Dose, and Dey Laboratories, Inc., Claimant-Appellant
Docket: 87-1392
Court: Court of Appeals for the Fifth Circuit; May 3, 1988; Federal Appellate Court
Dey Laboratories, Inc. (Dey) is appealing a summary judgment from the United States District Court for the Northern District of Texas, which determined that Dey's atropine sulfate inhalant (ASI) constitutes a "new drug" under the Federal Food, Drug, and Cosmetic Act (FDCA). The district court ruled that any existing consensus regarding ASI's safety or efficacy is not supported by adequate or well-controlled studies. Dey had sought to market ASI without FDA approval, arguing it was not a "new drug" as defined under 21 U.S.C. Sec. 321(p).
Dey initially submitted a new drug application (NDA) to the FDA in May 1983, but was informally notified by the FDA in September 1983 that the application was unlikely to be approved. Undeterred, Dey began marketing ASI in November 1983. The United States subsequently filed a forfeiture complaint against ASI on August 23, 1985, leading to Dey's claim on the seized product and the eventual granting of summary judgment in favor of the United States.
Under 21 U.S.C. Sec. 355(a), the introduction of a "new drug" into interstate commerce is prohibited without FDA approval. The definition of a "new drug" encompasses drugs not recognized as safe and effective by qualified experts or those that have not been used extensively outside of investigational contexts. The requirement of "general recognition" necessitates a consensus among experts based on "substantial evidence" as defined by the FDCA and FDA regulations. The case references prior circuit precedent regarding the standard for general recognition of drug safety and efficacy.
The court emphasizes that general recognition of a drug's efficacy is typically determined by expert consensus and substantial evidence. If the studies provided by the claimant are found to be conclusively inadequate according to statutory and regulatory standards, summary judgment is warranted. The absence of well-controlled investigations supporting the efficacy of Lutrexin categorizes it as a "new drug" under the relevant Act. Dey admits that the studies submitted to the district court did not involve the ASI it was marketing, referred to as "Dey's ASI." Dey seeks to use previously published studies on atropine sulfate inhalant to substantiate the safety and effectiveness of its product, but the court disagrees with this approach.
In United States v. Generix Drugs Corp., the Supreme Court ruled that a drug company must obtain FDA approval before marketing a product classified as a "new drug," even if it contains the same active ingredient as an approved product but varies in excipients. While Generix does not address whether two bioequivalent products with the same active ingredients but different excipients could be considered the same drug, it establishes that the FDA does not bear the burden of proving non-bioequivalence without prior relief requests. Dey claims its "generic ASI" is bioequivalent to Dey's ASI based on inhalation administration and cites 21 C.F.R. § 320.22(b)(4), which allows for waiving in vivo bioavailability evidence for certain products administered by inhalation, provided they contain the same active drug ingredient as an approved product.
Dey argues that a regulation by the FDA represents a judicial admission that inactive ingredients do not affect the clinical performance of inhalation solutions. However, the assertion is rejected on several grounds. First, the regulation does not bind the FDA because "generic ASI" does not meet the criteria of being a drug product with an approved new drug application. Second, the regulation only waives the need for in vivo bioavailability data, and this limited waiver cannot be interpreted as the FDA admitting that two drug products with the same active ingredient are legally equivalent, regardless of inactive ingredients. Third, the case does not involve a product attempting to "piggyback" on another FDA-approved product but rather seeks to rely on studies of separate, non-approved products. Even if there are factual questions regarding bioequivalence, the approval of drug "B" does not imply that studies of non-approved drug "B" suffice to classify drug "A" as a "new drug."
Consequently, Dey failed to provide substantial evidence for experts to recognize its ASI as safe and effective, rendering further findings on expert consensus unnecessary. Dey also invokes the "Bentex exception," suggesting that general recognition of a drug's efficacy might occur without the scientific support required for NDA approval. However, this exception is deemed inapplicable since Dey is not arguing for a lower threshold for demonstrating efficacy but rather for a broader scientific inquiry. Ultimately, the court concludes that the district court did not err in granting summary judgment, affirming the decision. The reference to a "paper NDA" is noted as irrelevant to the question of whether ASI qualifies as a "new drug" under the Act.
The reference to "Dey's ASI" in the presented material is found in the American Medical Association's Drug Evaluations, which only provides information on the clinical use of marketed drugs. Dey concedes that this single reference is not sufficient to meet the "adequate and well-controlled studies" requirement under the Act. Dey categorizes all atropine sulfate produced by others as "generic ASI," a term adopted for this opinion. This classification does not imply that the "generic ASI" prepared by different researchers is identical, nor does it suggest that any specific "generic ASI" is the same as "Dey's ASI," as each researcher created their own version during their studies. Stedman's Medical Dictionary defines "excipient" as an inert substance added to a prescription to provide form or consistency when administered as a pill. The First and Second Circuits have commented on the implications of the role of inactive ingredients in drug regulation, expressing reluctance to dismiss evidence regarding them and cautioning against district courts determining the therapeutic equivalence of drugs. Dey's counsel characterized the situation as "kafkaesque" during oral arguments.
