960 F.3d 1210
10th Cir.2020Background
- Genentech manufactured and labeled Herceptin multi‑dose vials as containing 440 mg trastuzumab and a reconstituted concentration of ~21 mg/mL; providers commonly could not withdraw the full labeled amount after reconstitution.
- Herceptin is shipped lyophilized (a solid cake) and must be reconstituted into a liquid for injection; the BLA listed 440 mg nominal per vial but also described the vial as “filled to deliver 400 mg.”
- FDA regulations require an accurate declaration of net quantity; 21 C.F.R. § 201.51(g) treats vial drugs differently depending on whether they are “liquid” (label expresses minimum quantity) or “solid” (label expresses accurate net weight).
- From 1998–2017 Genentech’s average trastuzumab per vial trended below 440 mg; FDA communications (2014–2017) urged label changes to reflect recoverable amount; Genentech ceased 440 mg multi‑dose production in 2017.
- Fourteen consolidated suits by cancer‑treatment providers alleged breach of express and implied warranties and unjust enrichment based on underfill/mislabeling; district court granted Genentech summary judgment on federal pre‑emption grounds (obstacle and impossibility); Tenth Circuit reversed and remanded.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Obstacle pre‑emption: do plaintiffs’ state‑law claims stand as an obstacle to federal objectives? | State law complements FDA standards; federal law requires minimum labeling for liquid vials, so state claims mirror federal misbranding law and do not obstruct Congress’s purposes. | State suits would conflict with FDA’s allowance for reasonable manufacturing/labeling variations and agency discretion; state claims would upset federal scheme. | No obstacle pre‑emption. The court held plaintiffs’ claims align with 21 C.F.R. § 201.51(g) (label must state minimum for liquid vials), so they do not stand as an obstacle. |
| Impossibility pre‑emption: could Genentech independently satisfy state duties without violating federal law? | Plaintiffs: Genentech could adjust within approved ranges (e.g., target concentration or fill) or use FDA procedures to change labeling; evidence shows historical ability to meet 440 mg. | Genentech: meeting a per‑vial 440 mg minimum would require major manufacturing and label changes that need prior FDA approval, making compliance with state law impossible. | No impossibility. The court found genuine factual disputes and insufficient evidence that changes would necessarily require FDA preapproval; Genentech failed to meet its heavy burden. |
| Regulatory classification: Is Herceptin a “liquid drug” or “solid drug” under §201.51(g)? | Plaintiffs: Because Herceptin is intended for injection after reconstitution, it is a liquid for labeling purposes and the label must express the minimum quantity. | Genentech: earlier regulatory history treated the product as a solid; §201.51(g) permits reasonable variation for solid drugs. | Herceptin is a “liquid drug” for §201.51(g) because the regulation applies to the form "intended for injection." Label must express minimum quantity. |
| Ability to change labeling/concentration (CBE process) | Plaintiffs: Genentech could have used existing FDA change processes (including CBE for some label changes) or targeted higher concentration within approved ranges to meet label claims. | Genentech: changing stated concentration or specifications requires prior FDA approval and thus cannot be done unilaterally. | Court: Genentech’s showing was inadequate; record does not support that CBE or other unilateral routes were unavailable. Summary judgment on this point was improper. |
Key Cases Cited
- Wyeth v. Levine, 555 U.S. 555 (2009) (state failure‑to‑warn tort claims not preempted by FDCA where manufacturer can independently change label and Congress did not clearly preempt state law)
- PLIVA, Inc. v. Mensing, 564 U.S. 604 (2011) (impossibility preemption requires showing it was impossible to comply with both federal and state law)
- Kisor v. Wilkie, 139 S. Ct. 2400 (2019) (limits Auer deference; courts must exhaust traditional tools before deferring to agency interpretation of ambiguous regulations)
- Merck Sharp & Dohme Corp. v. Albrecht, 139 S. Ct. 1668 (2019) (clarifies impossibility preemption standard and that burden rests on defendant)
- Riegel v. Medtronic, Inc., 552 U.S. 312 (2008) (contrast on express preemption for medical devices; context for FDCA preemption analysis)