Argument preview: Revisiting impossibility pre-emption

When state law and federal law conflict, the Constitution’s supremacy clause provides that federal law displaces, or pre-empts, state law. Pre-emption issues permeate prescription-drug safety litigation because the Food and Drug Administration regulates the safety and efficacy of prescription drugs under federal law, while state tort law provides the remedy for patients injured by the use of FDA-approved drugs. Prescription drug manufacturers frequently raise “impossibility pre-emption” as a defense in drug-injury cases, arguing that federal regulation would have prohibited the additional warnings plaintiffs allege state tort law required.

The Supreme Court has decided numerous pre-emption cases involving FDA regulations, bringing “impossibility pre-emption” into sharper focus over the past decade, starting with its 2009 opinion in Wyeth v. Levine. In Wyeth, a patient brought state tort claims against the manufacturer of an FDA-approved drug for injuries resulting from its failure to warn about the risks associated with intravenous administration. The manufacturer argued that the FDA’s extensive regulatory authority over its labeling made simultaneous compliance with state-law duties to warn impossible, thereby pre-empting the state tort claims. The Supreme Court held 5-4 that defendants asserting impossibility pre-emption had to produce “clear evidence” that the FDA would have prohibited an additional warning, and that Wyeth had not done so. Wyeth’s pre-emption formula has made several more trips to the Supreme Court. In Merck Sharp & Dohme Corp. v. Albrecht, set for argument on January 7, the Supreme Court will take yet another pass at honing the pre-emption principles it announced in Wyeth.

The Albrecht dispute originates with patients who allege they were injured by the FDA-approved prescription drug Fosamax, manufactured by Merck Sharp & Dohme. Over 1,000 patients have filed claims against Merck and other manufacturers alleging that Fosamax caused “atypical femoral fractures” and that the manufacturers failed to warn them adequately about the risks of these serious injuries. The Judicial Panel on Multidistrict Litigation consolidated these individual suits into a multi-district litigation (MDL), as it often does.

Merck argues that the FDA prohibits it from adding the warning that patients allege tort law requires, making compliance with both federal regulation and state tort duties impossible. Under federal law, the FDA must review and approve a prescription drug’s labeling, which includes warnings about side-effects and other risks. If the manufacturer wants to alter the approved labeling, it may seek the FDA’s approval for the change using the FDA’s “Prior Approval Supplement” (PAS) procedure.

This regulatory process for manufacturers to alter their warning labels plays a central role in pharmaceutical pre-emption after Wyeth. In Wyeth, the drug’s manufacturer had not sought FDA review or approval for the additional warning the plaintiff alleged was warranted. The Supreme Court in Wyeth held that, without having at least asked the FDA to consider the issue, the manufacturer had failed to meet its burden to produce “clear evidence” that the FDA would have rejected an additional warning. Thus, the plaintiff’s tort claims in Wyeth could proceed.

Merck, by contrast, submitted a PAS to the FDA, requesting to add language to the Fosamax label about fracture risk. In a letter to Merck, the FDA partially approved and partially rejected Merck’s proposed supplement. The parties disagree about the meaning of the letter and why the FDA rejected part of Merck’s proposed warning. Merck asserts that the FDA rejected the additional warning because the existing clinical data did not support it, which would have made adding the warning impossible. The plaintiffs argue that the FDA merely rejected Merck’s proposal to warn of “stress fractures” as inaccurate and could have approved a stronger warning on “atypical femoral fractures.” Merck’s pre-emption defense therefore turns on the meaning behind the FDA’s letter and the clarity with which the agency expressed its rejection.

Beyond a single FDA letter, the Fosamax litigation’s path to appeal raises existential questions about how to decide pre-emption questions and who should decide them. The MDL court convened a trial on the merits, and although the jury found the plaintiff had not proven Fosamax caused her injury, the MDL court also granted summary judgment to Merck on the ground that the plaintiff’s claims were pre-empted. After further briefing, the MDL court extended its pre-emption decision to the rest of the cases in the MDL proceeding. On appeal, the U.S. Court of Appeals for the 3rd Circuit vacated the district court’s grant of summary judgment on pre-emption and criticized the court’s extension of that decision to the whole MDL. The court of appeals held that Wyeth’s “clear evidence” standard and the longstanding jurisprudential presumption against pre-emption demand “clear and convincing evidence” that the FDA would have rejected a particular label change. Further, the court of appeals held that questions about the meaning behind the FDA’s rejection should be answered by a jury. The “how” question in the Fosamax litigation interrogates the contours of Wyeth’s “clear evidence” standard. The “who” question asks whether resolving ambiguity in the evidence should be a factual issue for a jury or a legal issue for a judge to decide.

In Merck’s view, the FDA’s rejection letter should conclusively answer the “how” question. Merck argues that the FDA’s statutory duties to act on newly discovered safety information and to work with manufacturers toward acceptable label updates render its rejection of a proposed warning conclusive proof that the agency would not have permitted a new warning. Because the FDA reviewed information about the risk of atypical femoral fractures from Fosamax and rejected Merck’s proposal to add a particular warning, it was impossible for Merck to have added the warning. Merck argues that in contrast to Wyeth, which set up a counterfactual inquiry about whether the FDA would have rejected a warning, the FDA’s actual rejection letter in this case eliminates the need for any such speculation.

To the extent that the FDA’s rejection letter is ambiguous about the basis for the rejection, Merck points to employee notes and emails with FDA personnel to suggest that the letter meant to reject the PAS based on insufficient data, rather than inadequate terminology. The United States, participating as amicus curiae on behalf of Merck, agrees that the FDA letter rejected Merck’s proposal based on insufficient data, but the government’s brief introduces no new evidence for that conclusion. The plaintiffs point to the language of the letter itself and challenge these explanations of the letter as implausible.

The dispute over the meaning of the FDA’s letter exposes a deeper issue of how much proof impossibility pre-emption requires. Wyeth held that defendants need “clear evidence” that the FDA would have rejected a particular warning. The stringency of Wyeth’s standard and what constitutes “clear evidence” of FDA rejection remain undefined. The 3rd Circuit interpreted Wyeth as setting an intermediate standard of proof for impossibility-pre-emption arguments and requiring that it be “highly probable” the FDA would have rejected an additional warning. The 3rd Circuit relied on the longstanding presumption against pre-emption, applied in Wyeth and numerous other cases, as a basis for a more demanding standard. Merck and the United States dispute that the presumption against pre-emption justifies a more demanding standard of proof, and they question the role the presumption should play in pre-emption analysis.

Beneath these interpretive questions about the standards for proving impossibility pre-emption lie more fundamental questions about who determines whether the FDA clearly would have rejected a warning. Although juries typically resolve factual questions and courts resolve legal questions, the line between those two categories can blur. Weighing conflicting statements and drawing inferences about FDA officials’ motivations, in the 3rd Circuit’s view, bear the hallmarks of factual questions that should be entrusted to juries. Merck and the United States, however, argue that the FDA’s decision on a PAS constitutes a federal agency action, whose meaning must be interpreted by courts under the Administrative Procedure Act.

Despite its technical and narrow focus on an FDA letter, this case encapsulates structural issues about pre-emption that permeate regulatory pre-emption arguments and drug-safety litigation: what lens should be applied to pre-emption questions and what role the presumption against pre-emption should play. The case also marks the first consideration of pre-emption issues by a newly constituted court, with Justice Neil Gorsuch replacing Justice Antonin Scalia (a dissenter in Wyeth) and Justice Brett Kavanaugh replacing Justice Anthony Kennedy (who joined the majority in Wyeth).