We have written before about the Supreme Court’s impossibility preemption decision, Merck Sharpe & Dohme Corp. v. Albrecht, 139 S. Ct. 1668 (2019) (Albrecht) (here, here, here, and here), highlighting some open questions and uncertainties that might come into play on remand. Albrecht held that impossibility preemption is a question of law for the court, not for the jury, “elaborated” on the “clear evidence” standard arising from Wyeth v. Levine, 555 U.S. 555 (2009) (Wyeth), and remanded to the Third Circuit for determination of the preemption issue. That court in turn remanded to the District of New Jersey and further directed the district court “to determine the effect of the FDA’s Complete Response Letter and other communications with Merck on the issue of whether the agency actions are sufficient” to find preemption.
We predicted that the decision on remand would be “interesting” and opined that the case for preemption was “strong.” We now have that decision, In re Fosamax (Alendronate Sodium) Prod. Liab. Litig., 2022 WL 855853 (D. N.J. Mar. 23, 2022) (Fosamax), and we were right on both counts.
Briefly, in September 2008, Merck submitted a PAS (Prior Approval Supplement) to the FDA. The PAS sought to add a warning of the potential risk of atypical femoral fracture, a low-energy stress fracture of the femur that had been theorized a potential side effect of bisphosphonate therapy like Merck’s Fosamax. Specifically, the PAS sought to add a warning in the Precautions and Adverse Reactions sections of the label. Those sections have different missions and different causality thresholds for inclusion of a particular risk. The former is for “clinically significant adverse reactions” and requires “reasonable evidence of a causal association.” The latter describes “undesirable effect[s], reasonably associated with use” and the threshold is “comparatively lower” — “some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event.”
In May 2009, the FDA issued a “Complete Response Letter” (CRL) advising Merck that it could not add a warning in the Precautions section, but, subject to rewording, could do so under Adverse Reactions. The CRL explained, in part, that the justification for the proposed Precautions statement was “inadequate.” Merck kept trying. The FDA issued a Drug Safety Announcement in March 2010 indicating that it did not see a clear causal connection but that it was reviewing data from Merck and other manufactures with an expert Task Force. As late as September 2010, the FDA and task force continued to question the sufficiency of evidence of causality. But, in October 2010, the FDA announced that it had completed its review and decided that all bisphosphonate manufacturers should add an FDA-drafted warning to the Precautions section.
Based on this record, a close reading of the CRL and its interpretation of Albrecht, the district court found “clear and convincing evidence” that Merck had “fully informed the FDA of the justifications for its proposed warning, which was adequate under state law and encompassed the injury Plaintiffs allege here, and the FDA, in turn, informed Defendant that it would not approve changing the Fosamax label to include that warning in the CRL.” Fosamax’s holding implies that Merck prevailed by overcoming a higher standard to establish preemption than Albrecht requires, which is good news for Merck on any appeal but raises additional questions for impossibility preemption in future cases.
First, as the court found (and noted that other courts have found), Albrecht does not require that the defendant propose a warning that the FDA has rejected. Rather, Levine’s predictive standard, asking whether the FDA “would have” approved the warning plaintiff contends state law required, remains viable. In any event, that Merck had proposed a warning that the FDA had rejected was compelling evidence that the FDA would not have approved a warning … because it didn’t.
Second, as Albrecht does not require a defendant to have proposed a warning, it follows that it does not require the defendant to demonstrate that a proposed warning was adequate under state law. Even if, as here, the manufacturer does propose a warning, it is unclear why, to establish impossibility, the warning needs to be found “adequate,” with all the analytical baggage that standard entails. All that should be required is that the warning plaintiff contends state law requires — i.e., the warning proposed by plaintiff — be one that the FDA would not have approved. In any event, the court found the Merck-proposed warning to be adequate.
Third, the court characterized its conclusion as based on clear and convincing evidence. That is not a standard endorsed by Albrecht — the Court found it unnecessary to define “clear evidence” in evidentiary terms because it was a question of law. Rather, the “clear and convincing evidence” standard is a creature of the Third Circuit decision that the Supreme Court overturned. Its appearance in Fosamax is enigmatic.
These nuances may be the product of the record, which was materially different from Levine, the only case in which the Supreme Court has applied the clear evidence standard. In Levine there had been no proposed warning and no explicit rejection of a warning about the risk. In a footnote (#10) Fosamax observed that Levine “does not instruct how this Court should interpret the meaning of an actual FDA decision on labeling …, which is the crux of this case.” Under the circumstances, the court was necessarily elaborating on Albrecht’s limited “elaboration” of the Levine standard.
Other points of interest:
- The court rejected Plaintiffs’ contention that the CRL lacked preemptive effect because it did not constitute “final agency action.” It explained that the FDA’s rejection of a warning does not need to be a final decision, only one that is within the agency’s authority such that it has the force of law. The court also clarified the impact of informal communications between Merck and the FDA, treating them as evidence relevant to interpreting the CRL rather than having any independent preemptive effect.
- The court’s interpretation of the CRL was critical because Plaintiffs primarily argued that the FDA rejected Merck’s PAS based on inadequacy of the proposed wording and that there was no impossibility because Merck could have obtained a warning by modifying the language. Because the court found that the FDA rejection “was predicated on insufficient evidence of a causal link between Fosamax and atypical femoral fractures,” no change in verbiage would have allowed Merck to warn of the risk. The court noted that the FDA’s amicus brief also supported its interpretation of the CRL.
- With a nod to the clarifying concurrence of Justice Alito in Albrecht, the court also invoked the “presumption of regularity” to reject Plaintiffs’ verbiage argument. The FDA’s affirmative obligation to protect public health and assure that warnings adequately disclose those risks supported by the available evidence undermined any inference that the PAS was rejected based on quibbles over phraseology rather than insufficiency of the causality evidence. And when the FDA was dissatisfied with the wording of the warning in the Adverse Reactions suggestion, it engaged in a curative dialogue with Merck rather than just reject the warning.
- In finding that the FDA was “fully informed,” the court recognized that the agency not only had Merck’s timely and fulsome submissions concerning the risk and causality, but it also had data from other bisphosphonate manufacturers. This reinforces that the focus should not be the manufacturer’s disclosure conduct, but on the FDA’s state of mind based on the total pool of information, including its own independent analysis and any investigation contributed by an expert panel. It also helped that the FDA’s amicus brief in Albrecht agreed that it was provided with the relevant risk data.
- The court’s analysis of the issues based on the record was, to say the least, thorough and rigorous. It emphatically confirms the wisdom of the Supreme Court assigning the impossibility issue and any subsidiary or subsumed factual findings to the court, rather than to the jury.
As we reported on Dolin v. GlaxoSmithKline, 951 F.3d 882 (7th Cir. 2020) (here), the analytical framework for evaluating impossibility remains relatively murky after Albrecht. In particular, the seemingly high bar applied in Fosamax for impossibility raises questions for future cases. Chief among them — did the Supreme Court contemplate a higher burden to establish preemption when the FDA is asked to add a warning than when it is not? That seems unlikely. But legal doctrines are built brick by brick, and the court’s analysis in Fosamax lays down a solid foundation.
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