The flimsy decision in In re Acetaminophen − ASD-ADHD Products Liability Litigation, 2022 WL 17348351 (S.D.N.Y. Nov. 14, 2022), leaves us scratching our heads. First, it claims to find “helpful guidance,” id. at *7, in Wyeth v. Levine, 555 U.S. 555 (2009), a prescription drug preemption case, despite the relevant drug(s) being over-the-counter (“OTC”), and thus approved under an entirely different FDA regulatory process. Since Levine is probably the worst prescription medical product liability decision to occur during the now 15-year lifespan of this Blog, when a citation like that appears, the result is not likely to be any good. Then, the decision makes a hash of the relevant administrative record, ignoring what the preemptive FDA regulations said in favor of material from the Federal Register that never actually made it into the regulations themselves.
ASD-ADHD is illustrative of the big difference that the “product liability” exception to express preemption for OTC drugs makes. 21 U.S.C. § 379r(e). Just compare the felicitous result in Truss v. Bayer Healthcare Pharmaceuticals Inc., 2022 WL 16951538 (S.D.N.Y. Nov. 15, 2022), that we blogged about not too long ago, with the monstrosity that follows here.
Unfortunately for the defendants (and probably a major reason the ASD-ADHD MDL exists in the first place), these plaintiffs allege personal injury, and thus fall within the “product liability” exception to express FDCA preemption. The absence of express preemption, however, does not affect the operation of implied preemption. Buckman Co. v. Plaintiffs Legal Committee, 531 U.S. 341, 352 (2001) (“neither an express pre-emption provision nor a saving clause bars the ordinary working of conflict pre-emption principles”). Thus, the moving defendant asserted implied preemption as grounds for dismissal in ASD-ADHD, by virtue of a conflict between the MDL plaintiffs’ claims and the FDA-approved “monograph” for the OTC drug − acetaminophen. “[F]or certain categories of drugs” – including this one – “the monograph system replaces the individualized NDA approval process with a rulemaking process.” 2022 WL 17348351, at *4. Further, in 2020 Congress took legislative action to remove what had been the worst obstacle to preemption in OTC drug litigation – that the FDA approval process had gotten bogged down and many such products were being sold under monographs that had ostensibly been “temporary” for decades.
The monograph system was reformed [in 2020]. The rulemaking process governing monographs was replaced with an administrative order process. The CARES Act also made existing [tentative final monographs (“TFMs”)] final orders if they met certain conditions.
2022 WL 17348351, at *4 (citations omitted). The perpetually “tentative” nature of FDA approval of acetaminophen had been the primary excuse for the no-preemption holding in In re Tylenol (Acetaminophen) Marketing, Sales Practices & Products Liability Litigation, 2016 WL 4538621 (E.D. Pa. Aug. 26, 2016), earning that case a place on our 2016 “worst case” list.
Unfortunately, however, notwithstanding that Congressional action, hostility to preemption still infects MDL-based litigation over acetaminophen. The claim in this MDL is that this drug purportedly causes autism in infants exposed in utero. Since no legitimate science has tied autism to any type of product exposure, that’s a red flag right there. Since the FDA requires drug warnings – including OTC drug warnings – to be based on science, not conjecture, this is precisely the type of litigation that preemption should preclude.
Erroneously, ASD-ADHD chose to rely most heavily on Levine, despite OTC drugs being governed by an entirely different approval scheme. The big difference is that the monograph process does not have any regulatory exception analogous to the “changes being effected” (“CBE”) exception that limits preemption in prescription drug product liability litigation under Merck Sharp & Dohme Corp. v. Albrecht, 139 S. Ct. 1668 (U.S. 2019), and Levine. Every aspect of OTC drug labeling is determined by what the FDA has approved in the “applicable” monograph for that drug:
- “[T]he statement of identity of the product shall be the term or phrase used in the applicable OTC drug monograph.” 21 C.F.R. §330.1(c)(1).
- An “applicable monograph” must also “describ[e] the ‘Indications’” for an OTC drug. Id. §330.1(c)(2).
- “Any other labeling under . . . shall be stated in the exact language where exact language has been established and identified by quotation marks in an applicable OTC drug monograph or by regulation.” Id.
The only exceptions are two lists of specific terms that may be “used interchangeably” or “deleted” as long as such changes “do not alter the meaning of the labeling that has been established and identified in an applicable monograph.” See Id. §§330.1(i) (79 interchangeable items), 330.1(j) (21 omittable terms). None of the terms in these two subparts have anything to do with autism or pregnancy warnings.
The FDA also promulgated an acetaminophen-specific OTC regulation. 21 U.S.C. §201.326(a)(1). This regulation specifies the precise language for “liver”-related warnings on acetaminophen-containing products marketed for adult use. Id. §201.326(a)(1)(iii)(A-C). That regulation also mandates a warning to users who were also being prescribed a particular blood thinning drug. Id. §§201.326(a)(1)(iii)(D). Nothing in §201.326(a)(1) has anything to do with autism or pregnancy.
The FDA’s general OTC regulations address pregnancy-related warnings separately, and provide:
(a) The labeling for all over-the-counter (OTC) drug products . . . shall contain a general warning . . . as follows: “If pregnant or breast-feeding, ask a health professional before use.” In addition to the written warning, a symbol that conveys the intent of the warning may be used in labeling.
(b) Where a specific warning relating to use during pregnancy or while nursing has been established . . . for a product covered by an OTC drug final monograph . . ., the specific warning shall be used in place of the warning in paragraph (a) of this section, unless otherwise stated in the NDA or in the final OTC drug monograph.
21 C.F.R. §201.63(a-b) (emphasis original). Once again, the obligation to provide any “specific” pregnancy-related warning for OTC drugs is dependent on the “monograph” for such drug. Moreover, as we’ve discussed before, as a general proposition, the FDA has exercised tight control over pregnancy-related labeling.
Thus, the FDA regulations applicable to OTC drugs are quite clear: Warnings for OTC drugs cannot deviate from what is required by the applicable monograph(s). Under Albrecht, these regulations and “final” monographs are the applicable “law” that requires preemption:
[T]he only agency actions that can determine the answer to the pre-emption question, of course, are agency actions taken pursuant to the FDA’s congressionally delegated authority. The Supremacy Clause grants “supreme” status only to the “the Laws of the United States.” U. S. Const., Art. VI, cl. 2. And pre-emption takes place only when and if [the agency] is acting within the scope of its congressionally delegated authority. . . . Federal law permits the FDA to communicate its disapproval of a warning by means of notice-and-comment rulemaking setting forth labeling standards, by formally rejecting a warning label . . .; or with other agency action carrying the force of law.
139 S. Ct. at 1679 (citations and quotation marks omitted). “[W]hatever the means the FDA uses to exercise its authority, those means must lie within the scope of the authority Congress has lawfully delegated.” Id. “[N]either agency musings nor hypothetical future [agency actions] constitute pre-emptive ‘Laws’ under the Supremacy Clause.” Id. at 1682 (Thomas, J. concurring). Nowhere – not once – did ASD-ADHD ever cite Albrecht, the Supreme Court’s most recent implied FDCA preemption decision.
In ASD-ADHD, there was never any dispute that the FDA had ever, by regulation, monograph, or anything else having the force of law, required that the labeling for OTC acetaminophen mention autism, or pregnancy. The decision concedes that
In 2009, the FDA finalized a monograph governing certain organ-specific warnings for labels of OTC drug products containing IAAA [“internal analgesic, antipyretic, and antirheumatic”] active ingredients. None of the warnings for acetaminophen under this regulation deal with pregnancy. The IAAA TFM became a final order effective March 27, 2020 under the CARES Act.
2022 WL 17348351, at *5 (citations omitted).
Further, the FDA itself considered “the safety of prescription and over-the-counter (OTC) pain medicines when used during pregnancy” in 2015. Here’s a link to the official statement on the FDA’s website. It addressed “[a]cetaminophen in both OTC and prescription products and the risk of attention deficit hyperactivity disorder (ADHD) in children born to women who took this medicine at any time during pregnancy.” FDA found insufficient scientific support for any label change. Id. (study “limitations” and “conflicting results . . . prevented us from drawing reliable conclusions”).
Thus, the preemptive “law” applicable to acetaminophen: (1) contained no provision allowing unilateral deviation from the warnings that the FDA required through applicable regulations and monographs; (2) did not, in either those regulations or the applicable monographs, require any warning about autism or pregnancy; and (3) the FDA itself rejected any change to the general pregnancy-related warnings for acetaminophen in 2015.
So, how could ASD-ADHD possibly rule against impossibility preemption?
By ignoring the “law.”
In particular, ASD-ADHD relied (as previously mentioned) on Levine while ignoring what the Supreme Court’s more recent decision in Albrecht held concerning the constitutional basis for preemption. The decision asked the right question – “could the manufacturer have unilaterally changed the label on [the drug] without violating the IAAA TFM, the regulations governing the Pregnancy Warning, and other applicable regulations?” 2022 WL 17348351, at *7. But, because it ignored the “law” and Albrecht, it got the wrong answer.
ASD-ADHD erroneously extended Levine, which dealt with a drug subject to the FDA’s CBE regulation, to OTC drugs, where no such regulation exists:
It is a foundational principle [this coming from Levine, although no citation was given] for OTC drugs, as it is for brand-name drugs issued through an NDA, that a manufacturer is responsible for the adequacy of the warnings on its drug label. The regulation of acetaminophen generally and the Pregnancy Warning regulation in particular do not alter that responsibility.
2022 WL 17348351, at *7.
That’s just not so. In Albrecht, which discussed Levine at length, the reason for prescription drug manufacturers “bear[ing] responsibility” for product labeling is specifically because they have the right and responsibility “to propose labeling changes,” either to the FDA or under the CBE regulation “without waiting for FDA approval.” 139 S. Ct. at 1682 (citations omitted). That system simply doesn’t exist for OTC drugs.
In examining the law applicable to OTC drugs, ASD-ADHD ignored what the applicable FDA regulations state, in favor of what they don’t state. “Critically, the IAAA TFM does not include any language to suggest that the requirements in the monograph are exclusive of any other warnings that a manufacturer may add to the label.” Id. (emphasis added). So where, then, does any unstated analogy to the CBE regulation come from in the OTC drug field?
Not from the “law.” Nowhere does any such “critical” exception to the supremacy of the FDA’s regulations and (now) final monographs appear in any applicable FDA regulation – or in any monograph. Instead, ASD-ADHD relies, on an unstated “expectation” in a 1982 FDA “statement” issued during the course of the agency’s notice and comment rulemaking for OTC drug regulations. Id. at *9. That expectation, however, is not reflected anywhere in the actual regulations themselves.
The 1982 Statement makes clear that by creating a “general warning,” the FDA intended to craft a warning that would be broad enough to apply to numerous OTC drugs and direct pregnant women to “advice that will enable [them] to make an informed choice. . . . The FDA added that “the general warning will usually not be required for products labeled with specific warnings against use by pregnant women, such as specific warnings developed in the course of OTC drug review” and incorporated into a drug’s monograph. . . . [This statement] does not address the ability of manufacturers to supplement the general warning with safety warnings specific to their OTC drug.
Id. The ASD-ADHD decision’s discussion of purported agency “intent” in FDA’s 1982 statement ended with a classic double negative:
Together, these textual and structural elements of the Pregnancy Warning do not suggest that manufacturers cannot add a more specific warning regarding acetaminophen in addition to the general warning that applies to all OTC drugs that are systemically absorbed.
Id. (emphasis added).
So, even with respect to the FDA’s 1982 statement, ASD-ADHD extracts conclusions from what the Agency didn’t say, not from what it did say. But here’s what the FDA actually did say about preemption back in 1982:
As stated in the proposed rule, a single national pregnancy-nursing warning with a specified text is necessary to ensure that OTC drugs are used safely and for their intended purposes. A single national warning will help ensure that consumers receive clear, unambiguous, and consistent information on the labeling of OTC drugs concerning use by pregnant or nursing women. Differing State requirements could conflict with the Federal warning, cause confusion to consumers, and otherwise weaken the Federal warning. FDA believes that differing State OTC drug pregnancy-nursing warning requirements would prevent accomplishment of the full purpose and objectives of the agency in issuing the regulation and that, under the doctrine of implied preemption, these State requirements are preempted by the regulation as a matter of law.
Pregnant or Nursing Women; Delegations of Authority and Organization; Amendment of Labeling Requirements for Over-the-Counter Human Drugs, 47 Fed. Reg. 54750, 54746 (FDA Dec. 3, 1982) (emphasis added). ASD-ADHD did not acknowledge this contemporaneous, direct authority.
Thus, even if the FDA’s 1982 statement in connection with the adoption of the 21 C.F.R. §§201.63, 330.2, could be considered “law” under Albrecht, which is highly questionable, that statement expressly supports – and does not impliedly undercut – implied preemption as argued by the defendant in ASD-ADHD.
ASD-ADHD further erred when it relied upon the “carveout for product liability” in §379(r) to deny preemption:
The [statute] prohibits state and local governments from establishing requirements for nonprescription drugs, 21 U.S.C. §379r(a), but includes a carveout for products liability suits. . . . Thus, the FDA has not “determined” that state law failure to warn claims are preempted.
2022 WL 17348351, at *9 (citations omitted). That reasoning, of course, is contrary to Buckman – cited above – and several other United States Supreme Court decisions. E.g., Sprietsma v. Mercury Marine, 537 U.S. 51, 65 (2002) (“Congress’ inclusion of an express pre-emption clause ‘does not bar the ordinary working of conflict pre-emption principles’”) (quoting Geier v. American. Honda Motor Co., 529 U.S. 861, 869 (2000)). The FDCA’s express preemption language simply does not affect the application of implied preemption.
Finally, the FDA’s 2015 acetaminophen determination also received short shrift in ASD-ADHD. Because “[t]he FDA noted that it would ‘continue to monitor and evaluate the use of pain medicines during pregnancy’ and would ‘update the public as new safety information becomes available’” that “statement does not alter the preemption analysis.” 2022 WL 17348351, at *10. This is precisely the sort of “hypothetical future” agency action that is not “law” and thus lacks preemptive effect under Albrecht. It also ignores basic preemption timing − that claims based on use prior to the 2015 determination (or some change in the science after that) could be preempted for lack of “newly acquired information.”
ASD-ADHD is thus legally unsupportable. It is not based on any express statutory or regulatory exception, analogous to the FDA’s CBE regulation that controlled in Levine, that allows OTC drug manufacturers to alter unilaterally the warnings mandated by the applicable, and preemptive, final monographs that govern acetaminophen. Nothing in any FDA regulation confers on manufacturers any unilateral power to augment OTC drug warnings to include information not permitted by their “applicable monographs.” Instead, the anti-preemption result in ASD-ADHD is wholly based on negative implications from FDA statements not constituting “law” as specified by Albrecht. Indeed, to the extent that the FDA’s 1982 statement, and/or the 2015 FDA’s rejection of any label change, are evidence of what the FDA thought about preemption in the acetaminophen context, those statements both explicitly support preemption of the claims at issue in ASD-ADHD.