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When Merck Sharp & Dohme Corp. v. Albrecht, 139 S. Ct. 1668 (U.S. 2019), was decided, we included it as both our best decision of 2019, and as our sixth worst case.  To us, Albrecht’s holding that all preemption issues are questions of law for the judge to decide overcame the uncertainties created by Court’s tinkering with the “clear evidence” preemption test.  We explained our attitude thusly:

In 95% of preemption cases (at least), we think defendants have the better side of the regulatory record, thus we should win most straight-up preemption arguments.  Courts can no longer cop out, or kick the can down the road, with the excuse of “disputed” facts.

Today’s case, In re Fosamax (Alendronate Sodium) Products Liability Litigation, ___ F. Supp.3d ___, 2022 WL 855853 (D.N.J. March 23, 2022), is further confirmation that our initial analysis of Albrecht was spot on.

Just as the previous Fosamax MDL judge had back in 2013, the current Fosamax MDL judge found all of the plaintiffs’ claims (only warning claims appear now to be at issue) preempted – only this time as a matter of law under Albrecht.  The decision is 87 pages long, but well worth the read.

We’ll try to boil down to a single paragraph the rather complex facts and regulatory history that produced Fosamax.  Even before the anti-osteoporosis drug Fosamax was FDA approved, its manufacturer was aware of a biologically plausible mechanism for that class of drug (“bisphosphonates”) to cause low-energy – later renamed “atypical” − femur fractures.  The manufacturer informed the FDA, but no evidence then established that risk as anything more than hypothetical.  Over the years, evidence that this risk was real accumulated, and the manufacturer provided a large quantity of material to the FDA.  In 2008, the manufacturer sent a lengthy prior approval supplement (“PAS”) seeking to add the risk of “stress fractures” to both the “adverse reactions” and “precautions” sections of Fosamax labeling.  The FDA’s April, 2009, formal “complete response letter” authorized the adverse reaction change, but not the precaution revision, due to insufficient data for the latter, and also turned down  “stress fracture” as a description of the risk.  At the FDA’s suggestion, the manufacturer withdrew that supplement, but kept trying.  Over a year and a half later, in October, 2010, industry-wide data finally convinced the FDA that the risk was scientifically established, and the agency ordered a label change adding atypical femur fractures to the precautions section of every drug in the bisphosphonate class.  2022 WL 855853, at *4-7.  In reality, things are a lot more complex, but the foregoing should be enough for our purposes.

Plaintiffs, of course, argued that the defendant manufacturer should not have waited for the FDA in actually making the label change.

The first intriguing aspect of Fosamax is its discussion of summary judgment standards when the determination is a question of law.  Instead of factual disputes being for a jury, they simply preclude preemption as a basis for summary judgment.  Id. at *10.  Fosamax placed more emphasis on the shifting burden of persuasion, first being on the moving party and then shifting to the non-movant.  Id.

Once the movant adequately supports its motion pursuant to Rule 56(c), the burden shifts to the nonmoving party to go beyond the pleadings and by [its] own affidavits, or by the depositions, answers to interrogatories, and admissions on file, designate specific facts showing that there is a genuine issue.

Id. (citation and quotation marks omitted).  “Credibility determinations are the province of the factfinder,” id., which in preemption cases after Albrecht is the judge.

In deciding all of the 500 or so Fosamax plaintiffs’ claims were preempted, Fosamax addressed the full panoply of post-Albrecht preemption questions – and the plaintiffs lost every one of them.

First, was the status of Wyeth v. Levine, 555 U.S. 555 (2009).  Plaintiffs claimed that Albrecht overruled Levine on the nature of “clear evidence” of preemption.  They lost.  The Levine standard was “not overrule[d], but merely clarified and expounded upon” in AlbrechtFosamax, 2022 WL 855853, at *10.  Thus, the Levine premise that preemption may be established by evaluating what the FDA “would have” done if faced with a label change, survives.  Id. at *12.  Plaintiff’s contrary position – that the “manufacturer must have actually requested a label change that the FDA then expressly rejected” – was “specious.”  Id. (emphasis original).  Fosamax observed that, of the “dozens” of decisions since 2019, not one court has interpreted [Albrecht] to establish a new standard for impossibility preemption requiring actual agency or manufacturer action.”  Id. at *12.

[Albrecht] uses the language of ordinary evolution rather than reversal and overruling. . . .  [T]he “universal” standard that a manufacturer need not submit a PAS and CBE to the FDA to preserve its preemption defense remains intact after [Albrecht]. . . .  In the end, it is, of course, the Supreme Court’s prerogative alone to overrule one of its precedents.  But it is difficult to reconcile the Court doing so when no party disputed [Levine]’s clear evidence standard on appeal, when the question before the Court was who should apply that standard, not whether the standard should survive, and when the Court itself held that its decision “flow[ed] from [its] precedents.”  139 S. Ct. at 1678 (emphasis added).  Accordingly, like all other courts having considered the issue, I find that [Albrecht] does not overrule [Levine].

Id. at *12-13 (other citations and footnote omitted).

Second, do the preemption holdings of the Supreme Court’s generic drug decisions in PLIVA, Inc. v. Mensing, 564 U.S. 604 (2011), and Mutual Pharmaceutical Co. v. Bartlett, 570 U.S. 472 (2013), apply to prescription drug preemption as well?  Answer:  yes.  “Essentially, a defendant must show that it could not have unilaterally changed its label in any way to add the warning required by state law.”  Fosamax, 2022 WL 855853, at *11.  See Id. (quoting Mensing regarding “possibilities” and impossibility preemption).  Likewise, Mensing’s holding that preemption does not turn on a “defendant’s failure to ask the FDA” for help applies to all drug litigation – meaning, in Fosamax, it had no obligation to seek further meetings with the FDA.  Id. at *29.

Plaintiffs’ argument is essentially that Defendant could have, perhaps, theoretically, changed the FDA’s decision had Defendant somehow insisted on engaging with the Agency or invoked an available procedural mechanism rather than withdraw its [supplement], but “the possibility of [that] possibility” is certainly not enough to “defeat[] pre-emption.”

Id. (quoting Mensing, 564 U.S. at 626 n.8) (emphasis original).

Third, the defendant “fully informed” the FDA about the relevant risk.  That question was not before the Supreme Court in Albrecht, and both the Supreme Court and then the Third Circuit remanded the case rather than make any factual determinations themselves.  Fosamax, 2022 WL 855853, at *13.  The “basic inquiry” is whether, at the time of the 2009 complete response letter, “the FDA had all the information it deemed necessary to decide whether to approve or reject the proposed warning.”  Id. at *14 (citation and quotation marks omitted).  An extensive record established that the manufacturer “promptly” responded to all FDA requests and provided everything that the FDA needed.  Id. at *14-17.  Notably, “Plaintiffs d[id] not point to any specific instance in which Defendant failed to provide any timely and relevant information.”  Id. at *17.  Moreover, the FDA itself, in an amicus brief filed in Albrecht, “agreed” that the defendant provided all “relevant scientific data” to the agency.  Id. at *15.  That carried the day:

Because the FDA alone is the arbiter of which data and information is or is not material to its decision to approve or reject a change to a drug’s label under [Albrecht], the FDA’s view of the evidence matters.

Fosamax, 2022 WL 855853, at *17 (citation, footnote, and quotation marks omitted).

Fourth, whether or not constituting “final agency action” for extraneous purposes, such as administrative appeals, the FDA’s complete response letter was preemptive “federal law” on which preemption could be based.  Such a letter reflects the “FDA’s complete review of the data submitted.”  21 C.F.R. §314.110(a)(3).  Plaintiffs’ contrary argument was “misplaced for several reasons.”  Id. at *18.  For one thing, Albrecht cited that same regulation, which authorized complete response letters, as an example of “formal” FDA power.  2022 WL 855853, at *18 (citing Albrecht, 139 S. Ct. at 1679).  Nor need an FDA action be “final” to be “formal” for preemption purposes under AlbrechtFosamax recognized that p-side argument for what it was – a bogus attempt to divest FDA actions of any preemptive effect:

[F]or preemption purposes, it is mostly irrelevant whether the [complete response letter] is of a merely tentative or interlocutory nature. . . .  [I]f Plaintiffs’ position were to prevail, no CRL could ever carry preemptive effect because all CRLs require some subsequent action on the part of the manufacturer, and preserve some procedural mechanism to further engage with the FDA, even if futile.

Id. (citation and quotation marks omitted).  Plaintiffs’ argument “would abrogate the very preemption effect of the federal regulation . . . that the FDA promulgated pursuant to congressional authority.”  Id. (citation omitted).

Fifth, while informal FDA communications are not preemptive in and of themselves under Albrecht, they can be quite relevant to a full understanding and accurate determination of the preemptive effect of FDA actions – such as a complete response letter – that are “formal” and thus do give rise to preemption.  Various FDA emails and other contacts demonstrated that the FDA issued its complete response letter because the FDA believed that the scientific data were insufficient to support the warning at issue, and was not merely a quibble about the term “stress fracture,” as plaintiffs contended.  Fosamax, 2022 WL 855853, at *19-24.  These materials demonstrated, among other things, that “the FDA clearly understood the type of fracture at issue.”  Id. at *22.

This point is important because it rejected plaintiffs’ position (which we’ve seen raised in other cases) that, after Albrecht, informal FDA communications should be disregarded altogether (at least when contrary to the plaintiffs’ preferred  position).

Defendant does not argue that the FDA’s informal communications themselves establish preemption, only that they “shed light on” the meaning and scope of the CRL, which is “Law” with preemptive effect.  I agree that it is appropriate to consider the communications for that limited purpose.

Id. at *24 (citation and quotation marks omitted).  “[I]nformal communications between the FDA and drug manufacturers should be considered in the preemption analysis.”  Id. (citation omitted).  The FDA’s formal complete response letter “does not tell the whole story without the proper context gleaned from other FDA communications.”  Id. at *25.  “In particular, it is appropriate to consider, and credit, the positions the FDA took in the amicus brief that the government filed in Albrecht itself.  Id. at *26.

Sixth, it matters that, under, 21 U.S.C. §355(o)(4)(A), the FDA was obligated to respond to any information it received, from any source, that demonstrated need for an additional warning.  Thus, contrary to plaintiffs’ argument, it was not “dispositive” that the complete response letter did not include “explicit discussion of the science” and “causation.”  Fosamax, 2022 WL 855853, at *26.

Plaintiff’s argument in this context must be rejected out of hand. . . .  [E]ven if I were to accept Plaintiffs’ position, one must assume that the FDA had reasonable evidence warranting a Precautions warning, but was so troubled by Defendant’s use of the term “stress fracture” that it rejected a warning without offering any suggestions or revisions.  To make such an assumption would effectively overlook the FDA’s raison d’etre to regulate drug safety, [and] its independent legal duty to notify a manufacturer as soon as it “becomes aware of new safety information that [it] believes should be included in the labeling of a drug” and “initiate discussions to reach an agreement … on labeling.”

Id. at *27 (citing §355(o)(4)(A)).  Since FDA actions are entitled to a “presumption of regularity,” Fosamax refused to credit any argument that assumed the FDA would not do what §355(o)(4)(A) required the agency to do.  That FDCA provision “imposes an ‘obligation to initiate a label change’ if the FDA believes one is warranted.”  Id.  Thus, the only valid inference why the FDA’s complete response letter did not require a label change had to be that the science was not there:

The more likely scenario is that the FDA’s actions taken in this case convey doubts that the Agency had about the underlying science, a deficiency no revision or edits could solve; hence, the Agency did not propose any.  The FDA’s subsequent inaction − it did not mandate a label change until October 2010, despite substantial ongoing review both internally and by the Task Force − confirms its then-existing perspective on the science, not that it was merely troubled by Defendant’s phraseology of its proposed warning.

Fosamax, 2022 WL 855853, at *27 (citations omitted).

This rationale also addresses a key, recurring point.  After enactment of §355(o)(4)(A), there was no longer such a thing as unexplained FDA inaction – as the Supreme Court relied on in Levine, 555 U.S. at 572 (the facts of which predated that amendment).  The affirmative obligation that the FDCA now imposes on the agency, when added to the previously discussed “completeness” requirement in §314.110(a)(2), precluded the negative inference from FDA inaction that plaintiffs advocated.  2022 WL 855853, at *27.  As Fosamax demonstrates, absent proof of withheld information, the inference now to be drawn from FDA rejection of a proposed warning is that the science did not support the warning.  Id. (only valid inference was that “the FDA was unconvinced of the causal link”).

Taken together, these provisions warrant the following inference as to the FDA’s intention when it issued the [complete response letter]:  the Agency did not believe there was reasonable scientific evidence of a causal association between bisphosphonate use and atypical femoral fractures, or else it would have suggested edits to that end, or simply mandated a warning using language that the FDA thought was more appropriate.

Id.  With courts required by Albrecht to evaluate preemption as a legal conclusion, the kind of p-side smokescreen that they tried in Fosamax should fail every time under the current regulatory scheme.

Seventh, in rejecting plaintiffs’ position that the manufacturer should have filed a “CBE” (changes being effected) warning change despite the FDA’s action, id. at *29, Fosamax held that there was no “newly acquired information” allowing the defendant to do so – confirming the lack of such information as an independent ground for preemption.  “The CBE process permits a drug manufacturer to unilaterally add a Precautions warning to its label, but only if ‘newly acquired information’ provides ‘reasonable evidence of a causal association of a clinically significant adverse reaction linked to a drug.’”  Id. (regulatory citations omitted).

The “newly acquired information” prong “is ‘part and parcel of the broader legal [preemption] question,’” id. (quoting Albrecht, 139 S. Ct. at 1680), thus “it is incumbent upon this Court to decide,” and is not a question of fact left to juries.  Id. (citation omitted).  “[T]he CBE process does not exempt the proposed change from the FDA’s substantive requirements, nor does it eliminate FDA jurisdiction.”  Id.  If the FDA had been “fully informed” of the basis for the proposed label change, as Fosamax had already determined, there could be no “newly acquired information” that would support a CBE label change:

[A]s a matter of procedure, in order for Defendant to proceed with the CBE process after the FDA rejected its PAS – [the manufacturer] was required to produce data indicating a greater-than-previously-known risk of [the relevant risk], which could establish “reasonable evidence” of a causal association. . . .  [E]ven though the FDA’s then-ongoing review was arguably more thorough than any review it might have conducted under the CBE process − the Agency was compiling data from multiple manufacturers . . . a variety of new reports, revisiting old ones, conducting its own analyses, and working with outside experts on the Task Force − it did not uncover definitive evidence linking [the drug] to [the relevant risk] to a greater extent than Defendant originally indicated.

Id. at *30.  The FDA being “fully informed,” as required by Albrecht’s “clear evidence” analysis, necessarily precluded the existence of “newly acquired information” that would support a CBE submission.  Id. at *30-31 (facts surrounding FDA review of Fosamax “impl[y] no new risks or correlations of which the FDA was not already aware”) (citations omitted).  That a clear evidence finding precludes “newly acquired information” is logical because the same FDA scientific standards apply to both.  “[T]he FDA’s review of Defendant’s CBE amendment would not have been any less rigorous than its review of Defendant’s PAS” (prior approval supplement).  Id. at *32.

Eighth, submission of a “futile” CBE supplement is not a prerequisite to preemption under Albrecht.

[A manufacturer] need not do so [“submit a CBE amendment, regardless of futility”] merely to preserve its preemption defense.  A manufacturer is under no obligation to use the CBE process to change the Precautions section of its label for any reason other than reasonable evidence of a causal association.

Fosamax, 2022 WL 855853, at at *32 (citations omitted).  To condition preemption on the filing of questionable CBE submissions with the FDA would be absurd.  “A contrary rule would incentivize manufacturers to submit a CBE amendment regardless of risk magnitude or scientific justification, which would impose an undue burden on the FDA.”  Id.  Encouraging manufacturers to seek baseless warnings is contrary to the FDA’s intent to prevent overwarning, as recognized in Albrecht.

[T]he FDA does not approve CBE amendments simply out of an abundance of caution, as Plaintiffs seem to suggest.  The Agency regulates drug labels for precisely the opposite reason: so as not to cause meaningful risk information to lose its significance. . . .  Indeed, while it is important for a manufacturer to warn of potential side effects, it is equally important that it not overwarn because overwarning can deter potentially beneficial uses of the drug by making it seem riskier than warranted and can dilute the effectiveness of valid warnings. . . .  Accordingly, Defendant could not have met the relevant CBE criteria had it submitted a Precautions warning through that regulation after the FDA rejected its PAS.

Id. (citations and quotation marks omitted).

Thus, the entire MDL (consisting only of warning-based claims at this point) was dismissed as preempted.  Fosamax is every bit as much of a preemption tour de force as was In re Zofran (Ondansetron) Products Liability Litigation, 541 F. Supp.3d 164 (D. Mass. 2021), which was our top-ranked trial court-level decision of 2021Fosamax is chock full of favorable preemption reasoning, so we recommend that all our readers who are involved in prescription drug preemption litigation sit down and read (or have an associate analyze) the whole thing.  It’s that good.