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Late last Friday, we learned of Hickey v. Hospira, Inc., ___ F.4th ___, 2024 WL 2513487 (5th Cir. May 24, 2024) (thanks, Dick!), becoming the first appellate decision holding that preemption applies to FDA approved prescription drugs that came on the market via the so-called “paper NDA” process.  See 21 U.S.C. §355(b)(2).  Hickey arises out of the Taxotere MDL, which has produced defense-friendly decisions in a number of areas.

The defense-friendly result in Hickey was entirely the doing of the court of appeals, since it reversed in large part a rather strained anti-preemption ruling by the district court − In re Taxotere (Docetaxel) Products Liability Litigation, 2022 WL 3042639 (E.D. La. Aug. 2, 2022), certification granted, 2022 WL 16923721 (E.D. La. Nov. 14, 2022).  Hickey was much more straightforward, applying the same implied preemption analysis to §355(b)(2) approvals as to any other prescription drug.

To start, here’s what a §355(b)(2) approval is – basically it’s an intermediate process between good old-fashioned new drugs and generics:

[It] is available for drugs that differ from the RLD [reference listed drug] in ways that are slight enough for the manufacturer to still rely on the RLD’s safety and efficacy data. Th[e] §505(b)(2) application need contain only that information needed to support the modification(s) of the listed drug.  Unlike [generic] drugs, §505(b)(2) drugs are not required to use the exact same labeling as the RLD.

Hickey, 2024 WL 2513487, at *2 (citations and quotation marks omitted).  That last sentence is key – the “sameness” requirement that supports extensive preemption in generic drug cases doesn’t apply to §355(b)(2) approvals.

But that hardly means, as the district court decision held, Taxotere, 2022 WL 3042639, at *15-16, that there’s no preemption at all.  Rather, there probably is – save for one factual (newly acquired information) nit that the court of appeals left for the MDL court to pick on remand.  Hickey, 2024 WL 2513487, at *8.  Otherwise, the Fifth Circuit held that the data plaintiffs relied on was far too shaky and tentative to support the label change that they sought:

In response to the FDA’s request, [one of the defendants] updated its label via the CBE regulation to add that “[c]ases of [plaintiffs’ claimed injury] have been reported.”  The FDA approved the update. . . .  In approving the changes, the FDA stated that “the sponsor’s simple statement that permanent cases have been reported is all that can reliably be said given the tremendous limitations of the data.”  In other words, the FDA did not conclude that the cases of [relevant injury] were necessarily caused by the [drug].

Id. at *3.

Getting to this result, the Fifth Circuit corrected a series of procedural missteps that had occurred below.

First, Hickey joined every other court we know of in rejecting the plaintiffs’ argument that there was no separate “newly acquired information” preemption prong, and that the only relevant question was the “clear evidence” issue that the Supreme Court addressed in Merck Sharp & Dohme Corp. v. Albrecht, 587 U.S. 299 (2019).  While no appellate decision had addressed preemption in the specific context of §355(b)(2), the Supreme Court’s extant prescription drug preemption cases were “informative.”  Hickey, 2024 WL 2513487, at *4.

PLIVA, Inc. v. Mensing, 564 U.S. 604 (2011), in particular established that the availability of the FDA’s changes being effected (“CBE”) regulation was necessary to avoid preemption.

Mensing did not reach the clear evidence test because the CBE regulation was not available to the manufacturers of the [generic] drug at issue, and the other two cases reached the clear evidence test but did so only after concluding that the CBE regulation was available ([Levine]) or after the manufacturer asserting preemption conceded its availability (Albrecht).  Accordingly, we conclude that the availability of the CBE regulation is a threshold issue to the clear evidence test.

Hickey, 2024 WL 2513487, at *8 (citing and following In re Zofran (Ondansetron) Products Liability Litigation, 57 F.4th 327, 336–37 (1st Cir. 2023); Knight v. Boehringer Ingelheim Pharmaceuticals, Inc., 984 F.3d 329, 338-41 (4th Cir. 2021); Gibbons v. Bristol-Myers Squibb Co., 919 F.3d 699, 708 (2d Cir. 2019); Dolin v. GlaxoSmithKline LLC, 901 F.3d 803, 815 (7th Cir. 2018); and In re Celexa & Lexapro Marketing & Sales Practices Litigation, 779 F.3d 34, 41 (1st Cir. 2015)).

Second, Hickey agreed with defendants that the entire definition of “newly acquired information” was essential to the preemption question, reversing the holding below that ignored the FDA’s express requirement that the information not only be “new” but also had to “reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA.”  2024 WL 2513487, at *5 (quoting 21 C.F.R. §314.3(b)).  The CBE regulation meant what it said, and plaintiffs could not short-circuit the FDA’s requirements to avoid preemption.  The decision below “held that ‘any post-approval data or analysis that would have demonstrated that the warnings in Defendants’ labels were insufficient would have qualified as newly acquired information under the CBE regulation.’”  Id.

That was error.  The decision misread the FDA’s explanation of this requirement.

Contrary to the district court’s conclusion, the FDA’s statement does not call for a departure from the textual definition of “newly acquired information.”  Instead, the statement twice clarifies that all requirements of the CBE regulation must be met before a manufacturer can unilaterally change its label.

Id. at *6 (emphasis added).  Nor did “practical concerns” – that is, the district court’s all-too-evident dislike of preemption – justify any “departure from the text” of the CBE regulation.  Id.  There were situations where “newly acquired information” could exist as to a paper-NDA drug, they just weren’t present in these cases.  Id. 

Therefore, in this case, for post-approval information to meet the requirements of “newly acquired information,” it must at least “reveal risks of a different type or greater severity or frequency” than the risks revealed in the scientific literature available to Defendants.

Id. (footnote omitted).

Third, having agreed with the defendants on all of the legal issues regarding preemption, Hickey reviewed five items of medical literature, the “cumulative” science, and adverse event reports from one of the defendants.  Id. at *7-9.  Four of the five literature items could not constitute newly acquired information as a matter of law on the appellate record because they failed to meet the aforesaid “different type or greater severity or frequency” requirement for the CBE regulation to apply.  Id. at *7-8.  The same was true of “cumulative” science.  The overall degree of risk was essentially the same, both pre- and post-approval:

Although the post-approval scientific literature continued to reveal instances of [the relevant claimed injury], that is not enough − it must also “reveal risks of a different type or greater severity or frequency” than the pre-approval scientific literature.  We conclude that it did not. . . .

Id. at *8 (citation omitted).  Nor did 43 adverse event reports amount to anything.  Unlike Levine there was a denominator to that numerator – “roughly 161,000 patients treated.”  Id. at *9.  That was “much lower than the incidence rates revealed by” the pre-approval literature, and could not possibly qualify as “newly acquired information.”  Id.

Only one piece of medical literature – an “abstract” (not even a full-fledged study) could conceivably qualify as newly acquired information, as defined in the FDA’s regulations – and then only if “minimal cases” were included.  Id. at *8.  A remand – explicitly limited to that item alone – was granted for consideration of preemption under the correct legal standards:

[W]e will only remand the question of the effect of the . . . Abstract results.  If the analysis of the same shows that it is not sufficient, then these Defendants are not liable to these particular Plaintiffs on their state law failure-to-warn claims.

Id. at *9.  That, frankly, doesn’t sound like much to us, but we can understand the appellate court’s desire to cabin the scope of the remand explicitly – no preemption-related funny business, such as trying to include additional medical literature, allowed.