824 F.3d 1062
D.C. Cir.2016Background
- Spectrum Pharmaceuticals developed levoleucovorin (Fusilev) and received Orphan Drug exclusivity for methotrexate-related indications until March 2015 and for a colorectal-cancer pain indication until 2018.
- Sandoz obtained expedited ANDA approval in March 2015 for a generic levoleucovorin labeled only for the Methotrexate Indications; its product is ready-to-use and sold in large 175 mg and 250 mg vials.
- Spectrum sued, claiming FDA unlawfully approved Sandoz’s ANDA because Sandoz intended its large-vial product to be used for the Colorectal Indication (Spectrum’s remaining exclusivity), and that FDA changed policy without explanation and failed to give notice before expediting review.
- The district court granted summary judgment for FDA and Sandoz; Spectrum appealed.
- The D.C. Circuit reviewed de novo and affirmed, holding FDA permissibly relied on the generic’s labeling (omitting the protected colorectal indication), did not change policy arbitrarily, and owed no pre-expedition notice because exclusivity was not withdrawn.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Whether FDA must consider a generic’s intended off-label use when Orphan exclusivity protects another indication | Spectrum: exclusivity bars FDA from approving ANDA if FDA knows generic will be used for the protected indication (intended use matters) | FDA: "for such disease or condition" refers to labeled indications; agency may rely on ANDA labeling | Held: FDA’s interpretation reasonable under Chevron; may base approval on labeled indications and permit labeling carve-outs |
| Whether FDA’s approval was arbitrary and capricious because it changed position on safety/appropriateness of large vials | Spectrum: agency previously associated large vials with colorectal use and warned against excessive vial sizes; approving large vials for methotrexate use is a departure without explanation | FDA: record shows agency long found large vials safe/effective; prior guidance was general and the agency reasoned through citizen petition denial | Held: No arbitrary change; FDA consistently evaluated safety and provided reasoned decision rejecting Spectrum’s claims |
| Whether FDA’s regulation requires inquiry into a manufacturer's subjective intent beyond its labeling claims | Spectrum: regulation bars approval of products "intended" for same use; FDA must probe subjective intent | FDA: objective intent can be determined from labeling claims in the ANDA; further inquiry discretionary and enforcement available later | Held: Agency reasonably may determine intended use from labeling in the ANDA and need not probe beyond it at approval stage |
| Whether FDA had to provide notice/opportunity before expediting ANDA review in response to a shortage | Spectrum: Orphan Drug Act requires notice before agency expedites review even if exclusivity not withdrawn | FDA: statutory/regulatory notice procedures apply only when exclusivity is withdrawn; expedited review is not withdrawal | Held: No notice required because FDA did not abrogate or withdraw Spectrum’s exclusivity period |
Key Cases Cited
- Purepac Pharm. Co. v. Thompson, 354 F.3d 877 (D.C. Cir. 2004) (de novo review of agency decision on summary judgment)
- Bristol-Myers Squibb Co. v. Shalala, 91 F.3d 1493 (D.C. Cir. 1996) (upholding labeling carve-outs for generics)
- Chevron U.S.A. Inc. v. Nat. Res. Def. Council, Inc., 467 U.S. 837 (1984) (deference framework for reasonable agency interpretations)
- Sigma-Tau Pharms., Inc. v. Schwetz, 288 F.3d 141 (4th Cir. 2002) (Orphan Act construed as protecting approved indications not off-label use)
- Abbott Labs. v. Young, 920 F.2d 984 (D.C. Cir. 1990) (textual fit and purpose inform reasonableness of agency interpretation)
- Teva Pharm. Indus. Ltd. v. Crawford, 410 F.3d 51 (D.C. Cir. 2005) (balancing innovation and affordability in drug regulation)
- FCC v. Fox Television Stations, Inc., 556 U.S. 502 (2009) (requirement that agency acknowledge and explain policy changes)
- Wash. Legal Found. v. Henney, 202 F.3d 331 (D.C. Cir. 2000) (FDA enforcement options for off-label promotion)
- Glob. Crossing Telecomms., Inc. v. Metrophones Telecomms., Inc., 550 U.S. 45 (2007) (upholding reasonable agency interpretations)