The advent of generic preemption in PLIVA, Inc. v. Mensing, 564 U.S. 604 (2011) (“Mensing”), and Mutual Pharmaceutical Co. v. Bartlett, 570 U.S. 472 (2013) (“Bartlett”), left plaintiffs who took generic drugs scrambling to invent bizarre, novel, and in some cases dangerous supposed causes of action. Before it went under, the erstwhile metoclopramide litigation (which produced Mensing itself) generated a wave of innovator liability claims – thankfully mostly unsuccessful, and allegations concerning failure to update generic labels. The latter was more successful in avoiding preemption but never got anywhere on the merits because it was simply an nonviable cause of action..
Another batch of plaintiffs left high and dry were those claiming injury from taking generic amiodarone. They have tried to squirm around preemption in essentially three ways. Theory one is that the generic manufacturers themselves promoted off-label use. Theory two is that they failed to ensure than an FDA-mandated medication guide actually made it into the hands of patients. Theory three is that generics benefited from the original branded manufacturer’s off-label promotion years earlier, and thus had some obligation to correct lingering misimpressions in the medical community left by that promotion.
We now count sixteen amiodarone cases in our generic preemption scorecard. There was one hot spot in Texas that allowed some of these claims to escape preemption on the pleadings, but those cases failed on the merits when plaintiffs failed to find any evidence of any FDCA violations. See Mitchell v. Wyeth Pharmaceuticals, Inc., 356 F. Supp.3d 634, 639 (W.D. Tex. 2018); Priest v. Sandoz, Inc., 2017 WL 7172504, at *11 (Mag. W.D. Tex. Dec. 28, 2017), adopted, 2018 WL 582532 (W.D. Tex. Jan. 17, 2018).
The other amiodarone cases have failed miserably at the outset. What lessons can they teach us?
First, all claims that seek to change warnings concerning generic drugs, however, they’re pleaded – read, disguised – by plaintiffs are preempted. “[W]hen the FDA has made a conclusive determination, positive or negative, as to the existence of a link between the drug at issue and some adverse health consequence, state law cannot mandate that a manufacturer include additional warnings beyond those that the FDA has determined to be appropriate to the risk.” Frei v. Taro Pharmaceuticals U.S.A., Inc., ___ F. Supp.3d ___, 2020 WL 1165975, at *4 (S.D.N.Y. March 10, 2020) (citation and quotation marks omitted). See also Marroquin v. Pfizer, Inc., 367 F. Supp.3d 1152, 1171 (E.D. Cal. Feb. 14, 2019) (“To the extent that these claims depend on [defendant] providing or communicating a warning that differs from the FDA approved label . . ., Mensing requires preemption and dismissal.”); Collette v. Wyeth Pharmaceuticals, Inc., 2018 WL 1258105, at *1 (N.D. Cal. March 12, 2018) (warning claims preempted; all other allegations too vague and must be repleaded); Bean v. Upsher-Smith Pharmaceuticals, Inc., 2017 WL 4348330, at *5 (D.S.C. Sept. 29, 2017) (“Defendants could not have changed the content of the warning label or Medication Guide and could not have disseminated additional warnings regarding ‘off-label’ use without violating federal law, [so] each of Plaintiff’s claims premised on Defendants’ alleged failure to warn is due to be dismissed as preempted.”), aff’d, 765 F. Appx. 934 (4th Cir. 2019).
Even of the lousiest case of the bunch, Arters v. Sandoz, Inc., 921 F. Supp.2d 813 (S.D. Ohio 2013), found warning claims, involving Dear Health Care Provider letters, preempted:
[Plaintiffs] claim that . . . defendants have a duty to warn consumers and physicians of known dangers of amiodarone in other ways. Plaintiffs argue that defendants should have taken steps other than changing the drugs label . . . to “adequately warn healthcare providers or the FDA of all adverse event reports and all warnings mandated by the FDA.” The plaintiffs in Mensing made a similar argument, that the generic manufacturers could have used “Dear Doctor” letters. . . . A generic drug manufacturer who warns of risks not present in the approved label or strengthens the warning through “dear doctor” letters or other means creates labeling that is not consistent with the approved label, and is thus inconsistent with the FDCA.
Id. at 819. See also Frei, 2020 WL 1165975, at *5 (defendant “could not have disseminated post-marketing warnings inconsistent with [branded] warnings and labeling − approved by the FDA − without violating federal law, and also could not have disseminated alternative post-marketing warnings without violating federal law, plaintiffs’ claims are preempted”); Stephens v. Teva Pharmaceuticals, U.S.A., Inc., 2013 WL 12149265, at *9 (N.D. Ala. Oct. 31, 2013) (throwing out “Dear Doctor” letter claim as “wholly preempted” under Mensing and Bartlett). That’s lesson number one, and that’s pretty obvious.
Even if these labeling claims weren’t preempted, they have serious problems – like adequacy as a matter of law. In Marroquin, the branded manufacturer the drug beat an unpreempted innovator liability claim on this basis:
[T]he FDA label clearly states that [the drug] is approved to treat two serious heart conditions and it is a drug of last resort because of its potentially fatal toxicities. More than once, pulmonary toxicity is clearly and expressly identified as the most dangerous toxicity/potential side effect. Percentages of those who experience pulmonary toxicity and the percentage of those who suffer fatal pulmonary toxicity is provided. Importantly, there is nearly two pages of warnings/information devoted entirely to pulmonary toxicity. These warnings are clear, do not appear to be inconspicuous, and appear to warn of the exact danger that tragically befell [the decedent]. Without elucidation from [plaintiff], the warning is adequate.
367 F. Supp.3d at 1162-63. So lesson number two, innovator liability can be beat the same way as any other warning claim.
Arters was more indulgent of plaintiff’s off-label promotion claims, claiming – with no support whatever – that the promoted off-label use was somehow “in violation of [state] law,” 921 F. Supp.2d at 820. Other decisions took a closer look at such claims and found them wanting. Off-label promotion allegations were recognized as just one more form of preempted warning/design claim in a second opinion in Stephens. Arters predated Bartlett, so since Bartlett claims that a drug was “not reasonably fit for [an] off-label purpose” were preempted as either a design defect or stop selling claim. Stephens v. Teva Pharmaceuticals, U.S.A., Inc., 70 F. Supp. 3d 1246, 1250 (N.D. Ala. 2014).
Further, most courts recognize that allegations of “inadequate post-marketing instruction” about off-label use are preempted as “a classic ‘failure to warn’ claim, despite plaintiffs’ representations otherwise.” Id. at 1251.
[T]o the extent those [off-label promotion] claims are not abandoned, they are due to be dismissed as preempted under Mensing and Bartlett because [defendant] could not have changed the content of the warning labels or Medication Guide and could not have disseminated additional warnings regarding “off-label” use without violating federal law.
McLeod v. Sandoz, Inc., 2017 WL 1196801, at *5 (D.S.C. March 31, 2017). “[A]llegations claim that Defendants’ alleged [off-label] promotion resulted in failure to properly warn and hence are preempted by federal law.” Connolly v. Sandoz Pharmaceuticals Corp., 2014 WL 12480025, at *6 (N.D. Ga. Dec. 23, 2014) (footnote omitted). Further:
Plaintiffs’ claims of negligence and negligence per se based on the alleged “off-label” promotion of amiodarone are impliedly preempted under Buckman because the duties Plaintiffs allege [defendant] breached regarding “off-label” promotion exist solely under the FDCA.
McLeod, 2017 WL 1196801, at *7. Thus, an off-label promotion claim concerning an otherwise non-defective drug is “preempted and cannot succeed as a matter of law.” Moore v. Zydus Pharmaceuticals (USA), Inc., 277 F. Supp.3d 873, 884 (E.D. Ky. 2017). Lesson three, use Buckman Co. v. Plaintiffs Legal Committee, 531 U.S. 341 (2001) (“Buckman“) to beat claims that plaintiffs crib from FDA regulations.
Eventually plaintiffs stopped claiming that the generic manufacturers themselves engaged in off-label promotion, and shifted to alleging that they had some sort of duty to correct or ameliorate the effects on the medical community of prior off-label promotion committed years earlier by the original branded manufacturer. In Bean, this latest version of an off-label promotion claim also failed.
Plaintiff’s negligence claims based on the alleged “off-label” promotion of amiodarone are impliedly preempted under Buckman because the duties Plaintiff alleges Defendants breached regarding “off-label” promotion exist solely under the FDCA. Plaintiff has not directed the Court to any . . . state law causes of action that parallel the federal safety requirements limiting the “off-label” promotion of drugs. Plaintiff’s claim for “off-label” promotion of amiodarone would not exist in the absence of the FDCA. Accordingly, Plaintiff’s claim for negligence and negligence per se based on Defendants’ alleged “off-label” promotion of amiodarone . . . is impliedly preempted under Buckman and due to be dismissed.
2017 WL 4348330, at *7. See McLeod v. Sandoz, Inc., 2018 WL 1456739, at *4 (D.S.C. March 23, 2018) (“McLeod II”) (dismissing amended complaint “for the reasons stated” in Bean).
Similarly, Frei, 2020 WL 1165975, held that any duty to “counteract” someone else’s prior off-label promotion failed. For one thing, it was preempted. Under Mensing there is no way a generic manufacturer could address prior off-label promotion without changing its label. “[E]ach alleged cause of action requires [defendant] to either change the labeling for amiodarone, change its design or formation, exit the market, or accept state tort liability.” Id. at *6 (quoting Bean). Under Buckman “the duties [plaintiffs allege defendant] breached regarding off-label promotion exist solely under the FDCA.” Id. (also quoting Bean). Lesson four is not to let off-label promotion claims off the hook, since the label itself would not exist without the FDCA.
Amiodarone allegations concerning medication guides first surfaced in Stephens, which pointed out why such claims don’t work. First, FDA “regulations require that Medication Guides be provided by a manufacturer to the distributor of a medication, not the end user.” Stephens v. Teva Pharmaceuticals, U.S.A., Inc., 70 F. Supp.3d 1246, 1252 (N.D. Ala. 2014). The manufacturer need only provide guides “in sufficient number” or the “means to produce” them to “distributors, packers, or authorized dispensers” – not end users. 21 C.F.R. §208.24(b)(1-2). “Critically, the regulation does not obligate a manufacturer to provide medication guides directly to patients or their agents.” Frei, 2020 WL 1165975, at *5. See Mitchell v. Wyeth Pharmaceuticals, Inc., 356 F. Supp.3d 634, 638 (W.D. Tex. 2018) (“contrary to Plaintiff’s contention, does not place a duty upon [a manufacturer] to take steps to ensure that the Medication Guides are distributed to patients beyond providing them in ‘sufficient numbers’ to distributors, packers, and authorized dispensers”); Moore v. Zydus Pharmaceuticals (USA), Inc., 277 F. Supp.3d 873, 880 (E.D. Ky. 2017). “[A]t the time a prescription drug is dispensed, it is the pharmacy (or authorized dispenser) that must ‘provide a Medication Guide directly to each patient,’ not the manufacturer of the drug.” Id. (quoting regulation). Lesson five is to study plaintiffs’ regulatory claims closely. Usually, the FDA regulations don’t stand for what plaintiffs claim.
Second, there is no corresponding state-law duty to circulate medication guides. Thus, a “claim for noncompliance with the federal regulation is preempted pursuant to Buckman.” Connolly v. Sandoz Pharmaceuticals Corp., 2014 WL 12480025, at *5 (N.D. Ga. Dec. 23, 2014). “Because the requirement to provide a Medication Guide . . . is based solely in the requirements of the FDCA . . ., and there is no parallel duty . . . under [state] law, Plaintiff’s claims based upon failure to provide a Medication Guide are preempted” under Buckman. Bean, 2017 WL 4348330, at *7. Time and time again, medication guide claims in amiodarone cases have fallen to Buckman preemption:
Although plaintiffs couch their failure to warn claims in traditional state tort law, it is clear the existence of the FDA’s medication guide regulation is the gravamen of these claims. There is no question [the] amiodarone medication guide is a “critical element” in this case. . . . Moreover, plaintiffs do not identify a parallel state law requiring [defendant] to make available to distributors an amiodarone medication guide. And when a plaintiff’s claims “exist solely by virtue of the FDCA . . . requirements,” state law claims are impliedly preempted.
Frei, 2020 WL 1165975, at *5 (quoting Buckman).
Because the requirement to provide a Medication Guide to distributors is based solely in the requirements of the FDCA and related regulations, and there is no parallel duty to provide a Medication Guide under [state] law, Plaintiffs claims based upon failure to provide a Medication Guide are preempted under Buckman. Stated another way, Plaintiffs’ claims against [defendant] for failure to provide a Medication Guide are preempted and due to be dismissed because the claims would not exist in the absence of the FDCA.
McLeod, 2017 WL 1196801, at *9 (citation omitted).
[Defendant’s] obligation to provide a medication guide arises solely from responsibility imposed by the FDCA. . . . Since [plaintiff’s] claim concerning receipt of the medication guide exists exclusively due to the federal regulatory scheme, her claim must fail as the cause of action is merely based upon alleged violation of the FDCA.
Moore, 277 F. Supp.3d at 881 (citations omitted). We’d already learned always to use Buckman, but amiodarone cases are good reinforcement of that lesson.
Frei tried to avoid preemption by claiming the same purported failures to provide medication guides as negligence per se. Didn’t work. Negligence per se based on FDCA requirements was Buckman preempted, since the FDCA “is not privately enforceable.” 2020 WL 1165975, at *6. Plaintiff also asserted the same claims under New York’s “little FDCA” statute. That gambit also failed:
In one breath, plaintiffs argue “they did not plead that any of the FDA warning[s] were inadequate,” yet in a second [they] argue [defendant] committed negligence per se by “misbranding” its product. Moreover, and again, the FDA approved the labeling and warning information associated with [the drug], and [defendant], a generic pharmaceutical manufacturer, has on ongoing duty to provide the same warning labels.
Id. at *7 (citation omitted). This is a reprise of lesson one – Mensing preempts all warning claims, no matter how plaintiffs try to disguise them.
Medication guide claims in amiodarone cases also fail because they directly implicate the learned intermediary rule – that prescription medical product manufacturers are legally required to provide labels to prescribers in the medical community, and those prescribers, not manufacturers, in turn provide warnings to their patients. Stevens, 70 F. Supp.3d at 1254 (“failure to allege [the] prescribing physician was not adequately informed about the risks . . . is fatal to plaintiffs’ claims”). The Fourth Circuit affirmed dismissal of medication guide claims in Bean on this basis (not reaching preemption):
In this case, [the prescriber] is the learned intermediary. As [plaintiff’s] physician he was best placed to evaluate [his] medical history and circumstances and to decide what information [plaintiff] needed to give informed consent to his treatment. Accordingly, as long as the [the prescriber] himself. . . .
765 F. Appx. at 936 (quoting Restatement (Third) §6). But because of Mensing, “It is uncontested that [the prescriber] received all the warnings required by federal law, and that these warnings are, on their own, adequate under state law.” Id. Thus,
The manufacturers made [the prescriber] aware of the risk . . . as they were required to do by federal law. That warning was never contradicted or diluted: There is no allegation that the manufacturers ever so much as insinuated that this risk was less severe that it really was. The only allegation is that the manufacturers misled [the prescriber] on an unrelated issue − the benefits of [the drug] − which does not come under the scope of failure to warn liability.
Id. at 937. Nor did the FDA’s medication guide requirement create any “exception” to the learned intermediary rule. Id. (“Such an exception would fly in the face of the FDA’s intent that the Medication Guide rule not ‘alter the duty, or set the standard of care for manufacturers.’”) (quoting 63 Fed. Reg. 66378, 66384 (FDA Dec. 1, 1998)).
Other amiodarone decisions agree. “[P]hysicians may and often do prescribe drugs for unapproved, off-label uses, as [plaintiff’s] physician allegedly did here. The decision to prescribe [a drug] for an off-label use rested solely with his physician. Within the context of prescription drugs, … [this jurisdiction] employs the learned intermediary doctrine.” Connolly, 2014 WL 12480025, at *5. Same result, slightly different take:
The application of the learned intermediary doctrine to Plaintiffs’ “off-label” promotion claims exposes a conceptual flaw in Plaintiffs’ case. To avoid preemption . . ., Plaintiffs state they do not challenge the adequacy or content of the FDA approved warnings for amiodarone. . . . Yet, in order to overcome the learned intermediary doctrine in this case, [the] prescribing physicians would essentially have to testify that they were unaware of a risk that Plaintiffs allege was adequately disclosed in the Medication Guide for amiodarone. Critically, Plaintiffs have not alleged that the prescribing physicians did not receive the Medication Guide or were otherwise unaware of its contents.
McLeod, 2017 WL 1196801, at *10. See McLeod II, 2018 WL 1456739, at *3 (learned intermediary rule barred claim where plaintiffs did not allege either lack of prescriber knowledge or anything else that would have “changed their decision to prescribe”). Lesson six is that, even when a defendant has a good preemption defense, do not ignore alternative state-law grounds.
Second, a medication guide doesn’t make any difference where a plaintiff is simultaneously alleging an off-label use. Off-label uses aren’t allowed in FDA-mandated medication guides to start with:
The plaintiffs fail to assert how the lack of a Medication Guide has any bearing on a claim of failure to warn for medication prescribed for an off-label use. [The complaint] suggests that the plaintiffs concede the “content” of the relevant warnings were sufficient, and they seek to recover solely for the failure of decedent to receive the Medication Guide.
Stephens, 70 F. Supp.3d at 1249. “[T]he court is struck by the inherent contradiction in plaintiffs’ allegations, specifically that they were not provided warnings for a use of [the drug] that was not within those warnings.” Id. at 1251. Doctors, not manufacturers, are responsible for off-label uses:
The plaintiffs fail to allege that but for defendants’ misrepresentations or suppressions about amiodarone, [decedent’s] doctor would not have prescribed this medication. Similarly, while plaintiffs allege [the decedent was not aware that his use of the medication was for an “off-label” use, the relevant inquiry is whether his physician was aware of this.
Id. at 1252 (citation and quotation marks omitted). Moore recognized the same problems in dismissing an express warranty case – a defendant doesn’t “expressly” warrant anything about an off-label use. “[Plaintiff’s] use of Amiodarone . . . was ‘off-label.’ Despite her alleged reliance, the express-warranty claims are without merit because the labels never explicitly warranted that [Amiodarone] was safe for” any off-label use. 277 F. Supp.3d at 887. Lesson seven is always to point out when a plaintiff’s claim just doesn’t make any sense.
We also spotted a couple of one-off arguments in amiodarone cases. In Frei the plaintiff pushed a consumer fraud claim under a New York statute. Consumer fraud has never been a good fit with the learned intermediary rule, and wasn’t in Frei:
[B]ecause a drug manufacturer’s duty to warn of a drug’s side effects runs to the doctor prescribing the drug, and not to the user of the drug, the issuance of [prescription] drug warnings . . . is not an act directed at consumers, and therefore any alleged deceptive act related to the issuance of those warnings is not a ‘consumer oriented’ act actionable under [the statute]. . . . To state a plausible . . . claim, a plaintiff must allege that the act, practice or advertisement was consumer-oriented and misleading in a material respect, and that plaintiff was injured as a result of such conduct.
2020 WL 1165975, at *7. That’s a repeat of an earlier lesson – pursue all state-law defenses.
Finally, one plaintiff tried to get around the problems with medication guide claims by claiming that the defendant was, in fact, a “distributor” rather than a manufacturer. Preemption barred that claim, as well, because mere distributors have no power to alter FDA-approved labels.
Outside of the context of fraudulent joinder and removal/remand, courts have extended Mensing to entities that merely distribute prescription drugs, be they generic prescription or brand-name prescription drugs. These cases recognize that mere distributors lack the ability to make any changes to an FDA approved label, rather only the holder of a New Drug Application (NDA) or the FDA itself can make any change to an FDA approved prescription drug label. In this respect, a mere distributor sits in the same shoes as a generic manufacturer, neither has the ability to alter or change an approved FDA warning label.
Marroquin, 367 F. Supp.3d at 1170 (citations omitted). That’s the last good lesson, and one that applies broadly to all prescription drug warning claims. All distributors now have a preemption defense under Mensing/Bartlett.