Prescription drug warnings require FDA approval which dictates what the manufacturer can say in the product’s labeling. An exception to the FDA-approval rule is the Changes Being Effected (CBE) regulation which allows a manufacturer to unilaterally change a drug’s warnings “to reflect newly acquired information” and where the revision would “add or strengthen a contraindication, warning, precaution, or adverse reaction for which evidence of a causal association satisfies the standard for inclusion in the labeling under [21 C.F.R. § 201.57(c).” 21 C.F. R. § 314.70(c)(6)(iii)(A). The CBE regulation is not an easy hoop to jump through and it shouldn’t be. FDA oversight of drug warnings and labeling serves several important objectives, including preventing over-warning that could lead to people not receiving appropriate care. So, when courts are faced with failure to warn claims in the prescription drug context, they should carefully consider what evidence plaintiff relies on to suggest a CBE labeling change was a viable option. The type of analysis seen in Warner v. Amgen Inc., 2025 U.S. Dist. LEXIS 26141 (D. Mass. Feb. 13, 2025).
The facts of Warner are tragic. Plaintiff’s son suffered from an arteriovenous malformation which caused him to experience frequent headaches throughout his life. Defendant manufacturers a drug approved for the treatment of migraine headaches. It operates by blocking calcitonin gene-related peptide (“CGRP”) receptors. Increased levels of CGRP are associated with migraines. One month after the drug was approved, plaintiff’s son received an injection of the drug. He suffered a massive seizure which led to brain damage and eventually to his death.
Plaintiff’s failure to warn claim was entirely premised on her allegation that defendant’s warnings should have included that individuals with a history of seizures and cerebrovascular disease or surgery, like her son, were excluded from the clinical testing done to obtain FDA approval. Plaintiff claimed that her claim was not preempted because defendant could have included such a warning pre-approval in its new drug application or defendant could have changed the warning post-approval under the CBE regulations. On defendant’s motion to dismiss, the court found both claims were preempted.
On plaintiff’s pre-approval warnings claim, she only had precedent outside the First Circuit to rely on. But as the court pointed out,
the First Circuit held that the FDA is “the exclusive judge of safety and efficacy based on information available at the commencement of marketing, while allowing states to reach contrary conclusions when new information not considered by the FDA develops.”
Id. at *21 (quoting In re Celexa and Lexapro Mktg. & Sales Pracs. Litig., 779 F.3d 34, 41 (1st Cir. 2015). So, in the First Circuit, the question is not whether a manufacturer could have proposed a different warning during the approval process, but “whether the FDA considered the safety and efficacy information giving rise to the need for that warning.” Id. In this case, it was clear that the FDA was aware of the exclusion criteria used in the clinical trials before it approved the drug and did not require defendant to include the full list on the drug’s label. Id. at *23. Therefore, plaintiff’s pre-approval failure to warn claim was preempted.
Plaintiff’s post-approval failure to warn claim completely hinged on whether defendant could have strengthened the label warnings through the CBE process. But remember, plaintiff’s son received his injection just one month after the drug was approved. So, the window for newly acquired information is quite small.
Plaintiff’s complaint did not allege any newly acquired information and therefore could not survive a preemption defense. But plaintiff moved to amend her complaint to add allegations related to nine articles which she contended constituted “newly acquired information of the cerebral risks presented by CGRP-blocking drugs, like [defendant’s].” Id. at *27. They did not.
None of the articles link the drug to any adverse event. They were about CGRP generally. So they could not show the “causal association” needed for a CBE labeling change. Nor were they “newly acquired information.” Three pre-date FDA-approval and the court found in implausible that FDA was not aware of these studies considered it “reviewed the world’s literature” before preparing its report on the risks of CGRP antagonism. Id. at *31. Of the six articles that post-dated approval, none discussed seizures as a risk. The court found all of the studies too attenuated to meet the rigors of the CBE regulations. For example, plaintiff could not show that an animal study about CGRP deficiency could be generalized to CGRP antagonist drugs. As both the pre- and post-approval failure to warn claims were preempted, the complaint was dismissed with prejudice and leave to amend was denied.