Case Name: ViroPharma, Inc. v. Hamburg, Civ. No. 12-0584 (ESH), 2012 U.S. Dist. LEXIS 56128 (D.D.C. Apr. 23, 2012) (Huvelle, J.)
Drug Product and Patent(s)-in-Suit: Vancocin® (vancomycin hydrocholride); No active patents at issue (last core patent expired in 1996)
Nature of the Case and Issue(s) Presented: The issue here concerns whether the United States Food and Drug Administration ("FDA") improperly denied an extended period of exclusivity for ViroPharma's drug based on a determination that its new conditions of use for the drug were minor and did not constitute a significant new use of the drug. ViroPharma manufactures the antibiotic Vancocin. On April 13, 2012, ViroPharma sued the FDA challenging the FDA's approval, on April 9, 2012, of three ANDAs permitting the marketing of generic versions of Vancocin. ViroPharma alleges that the FDA approved the three ANDAs (i) in violation of ViroPharma's statutory right under the Federal Food, Drug, and Cosmetic Act ("FFDCA"), 21 U.S.C. §§ 301 et seq., to a three-year period of exclusivity for Vancocin, extending through December 15, 2014; and (ii) based solely on in vitro bioequivalence testing in violation of the FDA's own regulations requiring in vivobioequivalence testing. ViroPharma filed a motion for a preliminary injunction seeking the immediate withdrawal of the FDA's approval of the three vancomycin ANDAs and precluding from approving any additional vancomycin ANDAs until ViroPharma's claims have been fully adjudicated. The Court denied the motion.
Why the FDA Prevailed: The court held that ViroPharma's motion for a preliminary injunction was unsupported. ViroPharma began submitting a series of filings to the FDA in 2006 with respect to statutory exclusivity and bioequivalence claims in relation to Vancocin. As one basis for its statutory exclusivity claim, ViroPharma cited the fact that on December 14, 2011, the FDA approved a supplemental new drug application ("sNDA") for Vancocin that fundamentally changed the labeling for the drug by adding new conditions of use relating to clinical studies, adverse reactions, clinical trials, nephrotoxicity, and geriatric use, by modifying Vancocin's indication, and by specifying a recommended dosing regimen. According to ViroPharma, those changes were based on new clinical safety and efficacy data to which it had exclusive rights. ViroPharma argued that Vancocin was entitled to a three-year period of exclusivity, running through December 15, 2014 under its interpretation of 21 U.S.C. § 355(j)(5)(F)(iv).
ViroPharma's bioequivalence claim relied on a more complicated regulatory backdrop. Because Vancocin is the only reference listed drug for vancomycin, any ANDA for generic vancomycin must establish bioequivalence to Vancocin in order to gain FDA approval. Before 2006 the FDA recommended using in vivo studies to establish the bioequivalence of generic versions of vancomycin. The FDA's initial recommendation for generic manufacturers to establish bioequivalence to Vancocin was to conduct in vivo studies with clinical endpoints. But generic manufacturers had notified the FDA that it was nearly impossible to do an in vivo bioequivalence study of a proposed generic for Vancocin. As recently as 2006, there had been no ANDAs submitted for the drug, and therefore, no generic competitors in the marketplace. In 2006, however, the FDA changed its bioequivalence recommendations for vancomycin and began to allow generic applicants to establish bioequivalence with in vitro studies.
The FDA determined that under the QI act (legislation relating to exclusivity periods for certain antibiotics), Vancocin was not entitled to Hatch-Waxman exclusivity because the sNDA that ViroPharma submitted did not constitute approval of a significant new use of the drug. The FDA also concluded that ViroPharma's argument that generic manufacturers must submit in vivo as opposed to in vitrostudies was unsupported by the statutory scheme. The FDA stated that it could require in vivo or in vitro testing, or both, on a case-by-case basis.
The court considered ViroPharma's arguments for a preliminary injunction. First, the court shot down ViroPharma's argument that the FDA's letter denying ViroPharma's Citizen's Petition was informal, and not subject to Chevron deference. The court began step one of the Chevron analysis and noted that the statute was likely ambiguous, because it did not clearly define the term "condition of use . . . approved before" the date of the QI Act's enactment. But the court noted that a statute's terms should be read in cotext, the statute's placement in and the overall statutory scheme should be considered, and the problem Congress sought to solve should be taken into account. It was clear to the court that the QI Act addressed the specific issue before it and that a drug manufacturer should not be entitled to renewed exclusivity when it makes minor changes to a drug's label.
Applying the second prong of its Chevron analysis, the court held that although the language appeared to be ambiguous, the FDA's interpretation of it was permissible. The FDA's interpretation was consistent with the legislative goal, which was partly was to prevent pharmaceutical manufacturers from abusing the approval process to extend the life of old active ingredient drugs. The court also found that the FDA's interpretation was in harmony with the principle that Hatch-Waxman's exclusivity provisions do not apply to all approved changes that are allegedly "new." The court concluded that once the FDA determined that § 355(v)(3)(B) imposed a limitation, it was well within the agency's discretion to set the bounds of that limitation. As such, the court concluded that the FDA's interpretation of the new Vancocin label, specifically, that it (i) did not constitute a significant expansion in the conditions of use of the product to new patient populations; (ii) did not support a changed indication; and (iii) did not prescribe a new dosing regimen, was proper under the statutory scheme.
The court next addressed ViroPharma's bioequivalence argument; whether the FDA violated its regulations when it granted generic vancomycin ANDAs approval without requiring submission of in vivo bioequivalence testing. The court opened its analysis of this issue by noting that decisions regarding bioequivalence of drugs fell squarely within the ambit of the FDA's expertise and merited a high degree of deference from the court. The court determined that, due to the fact that an agency's interpretation of its own regulations is controlling unless it is plainly erroneous or inconsistent with the regulation, ViroPharma was unlikely to prevail on the merits of its bioequivalence claim.
Last, the court dispensed with ViroPharma's argument that it would be irreparably harmed in the absence of a preliminary injunction. The court found ViroPharma's arguments to be highly speculative and unpersuasive. The court also held that the balance of equities favored the FDA and the generic-manufacturer intervenors. Last, the court concluded that the public interest would be served by denying the injunction, because it would lead to increased competition in the marketplace, and lower drug prices for consumers of vancomycin.
