Recently, FDA permitted generic manufacturers to carve out language from the labeling of generic versions of Hospira’s Precedex even though the generic labeling would infringe Hospira’s method of use patent. Under the Hatch-Waxman Act, ANDA applicants may “carve out” protected uses from a product’s labeling to prevent a brand manufacturer from precluding generic entry by adding protected indications to a brand drug’s label in a practice called “evergreening.” As long as the so-called “skinny labeled” generic is as safe and effective as the brand for all of the uses remaining on its label, the generic may receive an AB-rating and thereby considered a therapeutic equivalent to the brand drug for the labeled uses. The “carve out” uses are considered off-label uses. FDA determines the carve-out language based on the NDA holder’s use code in its Orange Book listing, which describes the approved use claimed by the patent; however, if the use code and label language are not identical, as is typical with a therapeutic use patent, the carve out analysis becomes a challenge because FDA does not read or construe patent claims. In these situations, deficient label construction in AB-rated skinny labeled generics may induce infringement of a brand patent listed in the Orange Book, leaving brand drugs protected by use patents in a potentially risky position.
In the case of Hospira’s Precedex, the brand drug was approved for two indications: (1) sedation of initially intubated patients in an intensive care setting; and (2) sedation of non-intubated patients prior to and/or during surgical and other procedures. It was protected by a use patent whose listed use code read: “intensive care unit sedation including sedation of non-intubated patients prior to and/or during surgical and other procedures.” If a use code was carved-out of a generic, there would be no remaining indication for the drug. Therefore, FDA requested public comment on its options and ultimately concluded that as long as any express reference to the protected was omitted from the labeling, the carve-out was permissible under the Hatch-Waxman regardless of the possible overlap of the use code for ICU patients and non-intubated patients generally. FDA essentially concluded that an FDA-approved generic drug could infringe a patent under the Hatch-Waxman. The Southern District of Maryland eventually upheld the carve-out decision as a proper exercise of the FDA’s authority under the Administrative Procedures Act (APA), but neglected to analyze Hatch-Waxman’s protection of method of use patents. See Hospira v. Burwell, No. GJH-14-02662, slip op. (D. Md. Sept. 5, 2014). This decision was in direct contravention of precedent. See AstraZeneca LP v. Apotex, Inc., 633 F.3d 1042, 1060 (Fed. Cir. 2010); Bone Care Int’l, L.L.C. v. Roxane Labs., Inc., 2012 U.S. Dist. LEXIS 80450, 33, 2012 WL 2126896 (D. Del. June 11, 2012); L.A. Biomedical Research Institute at Harbor-UCLA Medical Center v. Eli Lilly and Co., et al. at 6-7 (C.D. Cal. N0 2:13-cv-08567-JAK-JCG, motion dismissed); Caraco Pharmaceutical Labs. v. Novo Nordisk A/S, 132 S.Ct. 1670 (2012).
FDA’s decision may be lawful under the APA, but clearly authorizes an infringing use expressly prohibited by Hatch-Waxman and patent statutes. A more detailed analysis of this issue can be found here: The Patent Use Code Conundrum – or Why FDA Can’t Read (Patents)