Here is a question the First Circuit has now answered the wrong way — can a scientific paper published before the FDA approved a drug nonetheless qualify as “newly acquired information” that triggers a duty to change the warnings under the Changes Being Effected regulation? The Fifth Circuit said no last year in Hickey. The Fourth Circuit said no in Knight. The First Circuit’s own prior panel in Celexa said no. And now, in Warner v. Amgen Inc., — F.4th —-, 2026 WL 3033704 (1st Cir. Oct. 9, 2026), the First Circuit has said — maybe yes.

Warner is a hard case. A young man with a history of seizures and cerebrovascular disease died at twenty-five from cerebrovascular complications after taking a single dose of Aimovig, the defendant’s CGRP-receptor antagonist for migraine prevention. Id. at *1. There is no way to write about this one lightly, and we’re not going to try. But the law does not change because the facts are tragic, and the law the First Circuit announced here is, at least in part, a problem.

One quick regulatory note. Aimovig is a biologic, so FDA approval runs through a Biologics License Application (BLA), the biologics counterpart to an NDA. For our purposes the preemption and CBE frameworks are materially the same as on the drug side — there is no express preemption clause for either — and nothing in the analysis below turns on the drug/biologic distinction.

Here is the good news first. Plaintiff originally pleaded a garden-variety pre-approval failure-to-warn claim arguing that the FDA-approved label should have disclosed that clinical trials excluded anyone who had ever had seizures or cerebrovascular disease, and should have warned of the complications that befell her son. Id. at *4. The defendant moved to dismiss on impossibility preemption, pointing out that it was legally required to use the label the FDA approved, and had no unilateral power to change it. Id. The district court agreed, and so did the First Circuit.

The court held, as a matter of law, that a manufacturer’s ability to ask the FDA to include different label language is not the unilateral authority required to defeat an impossibility defense — and that this principle, long established post-approval under Wyeth, Mensing, and Albrecht, applies equally to pre-approval submissions, because a BLA (or NDA) is “by its nature, a request for agency approval.” Id. at *6. That is exactly right, and it is a useful statement of circuit law to have on the books.

The court then added belt to suspenders. The FDA plainly knew the trials excluded people with any history of seizure disorders or significant neurological conditions, and in fact considered and rejected a proposed cerebrovascular warning finding “insufficient evidence to include th[e] theoretical risk in labeling.” Id. at *7. So, the final approved label — with its particular description of the twelve-month exclusion and its silence about the lifetime exclusion — was itself the agency’s “determination” that the label was adequate, and “when the FDA formally approves a label stating one thing with full and obvious notice of the directly contrary position, one can read the approval as rejecting the contrary position.” Id. at *9 (quoting In re Zofran (Ondansetron) Prods. Liab. Litig., 57 F.4th 327, 343 (1st Cir. 2023)).

That is a clean, defense-friendly recitation of the pre-approval preemption rules. We’ll take it. Here is where the opinion starts to drift.

After the hearing on the motion to dismiss, plaintiff changed theories. In a supplemental brief, she submitted nine studies and literature reviews — most of them published before FDA approval — and argued that they were “newly acquired information” that would have allowed the defendant to invoke the Changes Being Effected procedure to unilaterally add a warning after approval but before her son was prescribed the drug. Id. at *5. The district court saw this for what it was and denied leave to amend as futile. The First Circuit reversed. Id. at *17. That alone is a disappointment; but the reasoning is worse.

First, the opinion treats pre-approval publication dates as largely irrelevant. “A study published prior to the approval of a drug or biologic’s label may still qualify as newly acquired information if it had not been ‘previously submitted’ to the FDA.” Id. at *15. Publication dates, the court said, are “not dispositive.” Id.

Compare that with where the rest of the field has landed on the same question. In Hickey v. Hospira, Inc., 102 F.4th 748 (5th Cir. 2024), the Fifth Circuit went the other way. The point there — the point that matters here — is that the pre-approval scientific literature is the baseline. It is what the FDA already had, or was obligated to have, when it made its labeling decision; by definition, it is not “newly” anything. The Fifth Circuit put the proposition in a footnote directly on point, flatly “reject[ing]” the argument “that an individual study that defendant was required to submit to the FDA before approval of Defendants’ drugs independently constitutes ‘newly acquired information.’” Id. at 759 n.8.

The Fourth Circuit got there first, and arguably further. In Knight v. Boehringer Ingelheim Pharmaceuticals, Inc., 984 F.3d 329 (4th Cir. 2021), the court held that information “could not have been ‘newly acquired’ because the FDA already knew about it.” Id. at 340 n.10. The Fourth Circuit specifically concluded that a document the plaintiffs cited “was not ‘newly acquired information’” because “it was submitted to the FDA before it approved Pradaxa.” Id. And even for information not formally submitted, the court held that an association “the FDA already knew of” when it approved the drug — “and nonetheless did not require the defendants specifically to warn of it in the label” — does not qualify as “newly acquired information.” Id. at 338-39. The animating principle is deference. Once something is in the public scientific literature, the agency with the specialized expertise and the statutory charge to evaluate that literature is presumed to have done its job. The question is not whether the defendant physically waved any particular paper in front of the FDA reviewers; the agency — not the manufacturer, and not a court on a motion to dismiss — owns the pre-approval record.

And here is the awkward part for the First Circuit — it had already said the same thing. In In re Celexa & Lexapro Marketing & Sales Practices Litigation, 779 F.3d 34, 41 (1st Cir. 2015) — which the Warner panel itself quotes — the court explained that the “newly acquired information” requirement “lets the FDA be the exclusive judge of safety and efficacy based on information available at the commencement of marketing, while allowing the states to reach contrary conclusions when new information not considered by the FDA develops.” Warner, 2026 WL 3033704, at *10 (quoting Celexa) (emphasis added). It is hard to square “exclusive judge of safety and efficacy based on information available at the commencement of marketing” with a rule that pre-approval publications are “newly acquired” whenever the record is silent on whether the agency saw them.

Second — and this is where it starts to sound like something else by another name — the court repeatedly leaned on the absence of record evidence that the FDA had seen the articles plaintiff relied on. “We also find no evidence in the record as it now stands that the [four studies] were brought to the FDA’s attention.” Id. at *15. Translation — at the pleading stage, we assume the FDA didn’t see this stuff, and the defendant has to come forward later to prove otherwise. That is a backdoor fraud-on-the-FDA theory, only without the discipline Buckman Co. v. Plaintiffs’ Legal Committee, 531 U.S. 341 (2001), would impose. Buckman, notably, is nowhere in the opinion. And that is the whole point of Buckman. Deciding whether the FDA was properly informed — whether it was fully in the loop or somehow hoodwinked — is the FDA’s job, not a federal court’s. Treating a plaintiff’s bare assertion that studies were not “brought to the FDA’s attention” as enough to defeat preemption at the pleading stage runs headlong into that principle.

Third, the First Circuit opened the door to animal studies as “newly acquired information.” The court was “not certain that the [animal] study fails to qualify as newly acquired information,” reasoning that FDA guidance permits “theoretical warnings ‘if the animal data raises substantial concern about the potential for … adverse reaction in humans.’” Id. at *16. We understand the hook — Aimovig was a first-in-class biologic and the FDA itself relied on animal data in approving it. Id. But using that fact to justify forcing manufacturers to chase every rodent paper into the CBE process is going to produce exactly the overwarning the agency keeps telling us it doesn’t want. The court even acknowledged earlier in the opinion that the FDA aims to “prevent overwarning,” including “theoretical hazards not well-grounded in scientific evidence [that] can cause meaningful risk information to lose its significance.” Id. at *2 (citations omitted). The two halves of the opinion do not entirely talk to each other.

Fourth, the causal-association prong took a hit. The court held that the regulatory definition of an adverse reaction does not “require[] that the inclusion of an adverse reaction in labeling be based solely on clinical studies of the drug itself,” id. at *18, and credited plaintiff’s theory that the newly acquired studies showed Aimovig was associated not with causing seizures, but with worsening the outcomes of seizures by weakening the blood-brain barrier. Id. at *17. That is a notably loose formulation of causal association for a motion-to-dismiss standard. The CBE regulation’s two causal thresholds — “reasonable evidence of a causal association” for warnings and precautions, and “some basis to believe there is a causal relationship” for adverse reactions, id. at *17 — were already generous. They are now even more so in the First Circuit.

Finally, we note what the opinion does not decide. The court flagged the “clear evidence” defense — that even if the four surviving studies had been submitted, the FDA would still have rejected the proposed label change — but observed that the defendant had “chosen not to rely on such an argument” at this stage, so the court didn’t reach it. Id. at *19. That defense remains fully available on remand, and given how specifically the FDA engaged with CGRP antagonism and the “world’s literature” on the subject, we would expect it to feature prominently on summary judgment.

The scorecard isn’t exactly even. Dismissal of the original pre-approval theory affirmed. Good. Clear circuit-level statement that a BLA/NDA submission is a request for agency action and cannot defeat impossibility preemption. Better. A ruling that pre-approval studies can be “newly acquired information,” that single animal studies may qualify, and that the required causal association does not need to involve the drug itself. Not good. And the whole thing is wrapped in a pleading-stage “we cannot say with certitude” posture that puts the manufacturer in the position of having to disprove, later, what plaintiffs barely alleged in the first place.

The bright spot is that this is a remand, not a verdict. The court itself noted that it was “inclined to read the record as the district court did” on the newly-acquired-information issue, and reversed only because, without expert testimony, it could not get all the way to “certitude.” Id. at *14. Plaintiff gets to replead. Based on what she has put on the table so far, we would not bet the farm on where she ends up.

But the broader doctrinal footprint is the thing to watch. The Fourth Circuit in Knight and the Fifth Circuit in Hickey — and, before them, the First Circuit’s own panel in Celexa — had put the field on reasonably firm ground that information already in the FDA’s hands (or in the public scientific literature) at the time of approval is not “newly acquired” when a plaintiff later rediscovers it. Warner nudges that ground. If a published-but-not-formally-submitted study predating approval can still ground a CBE claim, “the exclusive judge of safety and efficacy” is no longer the agency — it is the lawyer with the better literature search. We hope the First Circuit, or the next panel to grapple with this on a fuller record, reels this one back in.