57 F.4th 327
1st Cir.2023Background
- Zofran (ondansetron) is FDA‑approved for chemotherapy/radiation/postoperative nausea but commonly prescribed off‑label for pregnancy; GSK marketed it until 2015 and did not include a fetal‑harm warning on the label.
- At initial FDA approval GSK submitted several UK and one Japanese animal reproductive studies; the FDA reviewed those studies and categorized Zofran as Pregnancy Category B (no evidence of teratogenicity).
- Plaintiffs rely on three Japanese animal studies (not originally submitted to the FDA) and experts who interpret those studies as showing teratogenic signals; plaintiffs sued in an MDL alleging state‑law failure‑to‑warn and fraudulent marketing theories.
- Regulatory context: manufacturers can seek label changes via PAS (prior approval) or unilaterally via CBE (Changes Being Effected) for "newly acquired information" showing reasonable evidence of a causal association; FDA can also act or be petitioned.
- The district court granted summary judgment for GSK on impossibility preemption grounds; the First Circuit affirmed, holding the Japanese studies were not "newly acquired information" and, alternatively, that the FDA's fully informed approval of the later label constituted clear evidence it would have rejected the proposed warning.
Issues
| Issue | Plaintiffs' Argument | GSK's Argument | Held |
|---|---|---|---|
| Were the three Japanese animal studies "newly acquired information" enabling CBE? | The Japanese studies revealed teratogenic signals and differed materially from the studies previously submitted, so they were newly acquired. | The studies showed no statistically significant causal findings and reported risks were of the same type/frequency as studies already before the FDA. | Not newly acquired: the studies did not reveal new types/greater severity or frequency of risk compared to prior submissions. |
| Could GSK have used the CBE route to add a stronger fetal‑harm warning? | Yes, if the studies qualified as newly acquired, CBE was available to strengthen warnings based on reasonable evidence. | CBE unavailable because the studies were not newly acquired and lacked reasonable evidence of causal association. | CBE unavailable for the three studies because they do not meet the regulatory definition of newly acquired information. |
| Did the FDA, once fully informed, provide "clear evidence" it would have rejected the proposed warning? | No; plaintiffs contend there is no clear evidence the FDA would have denied a stronger animal‑data warning. | The FDA, fully informed of the studies and contrary expert views, approved updated labeling stating animal data showed no significant fetal effects — which rejects plaintiffs' proposed warning. | Held for GSK: the FDA’s formal approval, after being fully informed, is agency action with force of law and constitutes clear evidence it would have rejected a contrary label. |
| Does federal law preempt plaintiffs’ state failure‑to‑warn claims? | Plaintiffs: preemption not established because CBE might have been available and the FDA would not clearly have forbidden the warning. | GSK: federal law preempts because it was impossible to comply with both state law and federal labeling constraints. | Affirmed: plaintiffs’ state claims are preempted (no newly acquired information; alternatively, clear evidence FDA would have denied the warning). |
Key Cases Cited
- Wyeth v. Levine, 555 U.S. 555 (2009) (manufacturer may be liable under state law absent clear evidence FDA would have rejected a proposed label change)
- Merck Sharp & Dohme Corp. v. Albrecht, 139 S. Ct. 1668 (2019) (clarifies that the question whether FDA would have disapproved a label change is for the judge and requires agency action carrying force of law)
- Mutual Pharm. Co. v. Bartlett, 570 U.S. 472 (2013) (impossibility preemption where compliance with both federal and state requirements is impossible)
- In re Celexa & Lexapro Mktg. & Sales Pracs. Litig., 779 F.3d 34 (1st Cir. 2015) (discusses newly acquired information and CBE context in preemption analysis)
- Knight v. Boehringer Ingelheim Pharms., Inc., 984 F.3d 329 (4th Cir. 2021) (examined whether information qualified as newly acquired information under CBE regulations)