Gordon D. Todd is a Partner in the Washington, DC office of Sidley Austin LLP, and J. Manuel Valle and Alaric R. Smith are Associates in the firm’s Washington, DC office.*
Drug manufacturers can breathe a sigh of relief following the Fourth Circuit’s recent decision in Knight v. Boehringer Ingelheim Pharmaceuticals, clarifying that scientists’ “hypotheses, differing viewpoints[,] and even preliminary conclusions” expressed during research, testing, and analysis of a drug’s risks are not, “without more,” the sort of “newly acquired information” that can defeat a federal preemption defense under the FDA’s Changes Being Effected (“CBE”) regulation. 984 F.3d 329, 340 (4th Cir. 2021). Adding to a growing body of law recognizing that internal deliberations do not commit a drug manufacturer to a particular scientific conclusion, Knight offers the most detailed circuit court analysis of this issue to date and mandates “careful review of the record . . . to determine whether a conclusion [about a drug’s risks] has been reached.” Id. at 341 (emphasis added). By resolving this issue as a “question of law,” moreover, Knight underscores the broad implications of the Supreme Court’s 2019 decision that “a judge, not the jury, must decide the pre-emption question.” Merck Sharp & Dohme Corp. v. Albrecht, 139 S. Ct. 1668, 1676 (2019).
Background
Knight involved state law claims that Boehringer provided inadequate warnings about the risks of its drug Pradaxa. 984 F.3d at 332. A blood thinner, Pradaxa reduces the risk of stroke, but can also create “the risk of uncontrollable, and potentially fatal, bleeding.” Id. In Knight, the plaintiffs’ mother suffered a gastrointestinal bleed and died from complications after having taken Pradaxa for over a year. Id. Adequate Pradaxa warnings, the plaintiffs claimed, could have prevented her death. Id.
The Federal Food, Drug, and Cosmetic Act ordinarily preempts such claims because the FDA approves risk information in drug labeling and manufacturers generally cannot change warnings unilaterally. See Albrecht, 139 S. Ct. at 1672. Under the CBE regulation, however, a drug maker can unilaterally “add or strengthen” a warning in labeling “to reflect newly acquired information” about a drug’s risks. See 21 C.F.R. § 314.70(c)(6)(iii)(A). Thus, plaintiffs can overcome federal preemption by proving that the CBE process was available—unless, that is, the drug maker can show the FDA would have disapproved the proposed CBE labeling change. See Albrecht, 139 S. Ct. at 1679.
The Knight plaintiffs contended that Boehringer’s post-FDA-approval research had revealed “newly acquired information” about Pradaxa’s risks for patients with impaired kidney function and the need for those patients to monitor Pradaxa concentration in their blood. 984 F.3d at 338. The FDA had approved Pradaxa without any such monitoring requirement—a major selling point of the drug highlighted in Boehringer’s advertising. But the plaintiffs claimed that a study published by Boehringer scientists (the “Reilly Paper”), along with the preliminary results of that study, indicated blood monitoring should be required because there was a Pradaxa blood concentration range within which the drug’s benefits would outweigh its risks. Id. at 334–35. The Reilly Paper itself found that there was no optimal Pradaxa blood concentration range, but an early draft of the study had reached the opposite conclusion. Id. at 335. The plaintiffs highlighted allegedly incriminating internal emails discussing the study’s initial findings and the potential marketing implications of requiring blood monitoring going forward. Id. at 335.
The district court agreed with the plaintiffs that this evidence constituted “newly acquired information” Boehringer could have used to revise Pradaxa’s labeling via the CBE process, and sustained a jury award of compensatory and punitive damages. Id. at 336–37.
The Fourth Circuit’s Decision
The Fourth Circuit reversed. As an initial matter, the court noted that, under Albrecht, whether Boehringer had “newly acquired information” was a question of law. 984 F.3d at 337 n.8. Reviewing the issue de novo, therefore, the court held that neither the Reilly Paper itself nor its preliminary conclusions qualified as “newly acquired information” under the CBE regulation.
Regarding the Reilly Paper, the court first held that because it was published after the plaintiffs’ mother’s injury, the study could not have prevented that injury. Id. at 338. What is more, “newly acquired information” must “reveal risks of a different type or of greater severity or frequency than previously included in submissions to the FDA.” Id. at 338 (quoting 21 C.F.R. § 314.3(b)). Because the FDA was already aware of the risks identified in the published Reilly Paper from prior Boehringer submissions—e.g., the increased risks for patients with impaired kidney function—and because the Reilly Paper concluded that there was no optimal blood concentration that would require monitoring, it could not qualify as new. Id. at 339.
Nor were the Reilly Paper’s preliminary conclusions “newly acquired information.” This was a “more difficult question,” the court explained, because an initial draft of the Reilly Paper had indicated blood monitoring might be necessary, and scientists’ internal emails noted that these preliminary findings were “not the ones currently wished for by marketing.” Id. The court nevertheless rejected plaintiffs’ reliance on Boehringer’s preliminary findings for two reasons. First, those findings were tentative, as evidenced by the scientists’ stated need for further research and analysis to “see where this paper ends up” before drawing any definitive conclusions about the need for blood monitoring. Id. at 349. Second, further research and analysis did, in fact, result in a “different conclusion,” which “the scientific and regulatory community accepted” when the Reilly Paper “was published, peer-reviewed and submitted to the FDA,” which “continued to approve labels [sic] with no monitoring requirement.” Id. at 340.
While thus requiring that “newly acquired information” consist of sufficiently definitive findings, the court qualified its holding in two respects. First, new evidence need not take the form of a “final, peer-reviewed publication of an analysis” because “[s]ome findings may be revealed instantly” with no need for further study. Id. Second, “peer review and publication of an article do not themselves prevent contrary findings from qualifying as newly acquired information” if there is evidence—which in Boehringer’s case there was not—that a drug company ignored contrary evidence in bad faith. Id.
The court also emphasized the policy underlying its analysis—namely, that “[i]t is imperative for the scientific process that open dialogue . . . take place during an analysis and drafting of a paper.” Id. at 340. If drug companies faced liability based on “hypotheses, differing viewpoints and even preliminary conclusions,” the court explained, “companies might discourage the open dialogue needed to reach the best results,” or “unnecessary warnings might flood labels and distract from real risks.” Id. at 341.
Significance
The Fourth Circuit’s decision strengthens drug makers’ preemption arguments going forward and diminishes the legal risks attendant in a vigorous and robust drug development program. Knight is consistent with other circuits’ more limited analyses of the “newly acquired information” question. See In re Avandia Mktg., Sales & Prod. Liab. Litig., 945 F.3d 749, 760 (3d Cir. 2019) (CBE process available based on “completed” study); In re Celexa & Lexapro Mktg. & Sales Practices Litig., 779 F.3d 34, 42 (1st Cir. 2015) (CBE process not available where plaintiffs failed to allege that cited articles relied on new data). The Fourth Circuit’s more nuanced analysis, however, may prove persuasive in “caution[ing] against a quick trigger in determining the existence of newly acquired information.” 984 F.3d at 340.
Finally, the Fourth Circuit’s de novo review of the factual record underscores the significance of Albrecht’s holding that “a judge, not the jury, must decide the pre-emption question,” even when contested facts “prove relevant to the court’s determination.” 139 S. Ct. at 1679–80. Whereas Albrecht focused on the FDA’s disapproval of the CBE labeling change, Knight extends the Supreme Court’s holding to require that judges, not juries, determine the presence of “newly acquired information.” Should Knight’s reading become the norm—and thus far no court has construed Albrecht narrowly—it will strengthen manufacturers’ hand in avoiding the costs of trial in the CBE context.
*This article has been prepared for informational purposes only and does not constitute legal advice. This information is not intended to create, and the receipt of it does not constitute, a lawyer-client relationship. Readers should not act upon this without seeking advice from professional advisers. The content therein does not reflect the views of the firm.