US Pharm. 2011;36(9):49-51.
Overshadowed by the Supreme Court ruling in June that data mining for prescriber-identifiable data is legal,1 on that same day another case was decided by the Court that might have far-reaching liability potential that should be a concern for pharmacists. The case, Pliva, Inc. v. Mensing,2 draws a distinction between the liability for labeling information for brand-name drugs and generic equivalents. The case was a consolidation of appeals in three cases where the Fifth and Eighth Courts of Appeals ruled in favor of the injured patients.3 This Supreme Court Opinion, in a 5-4 vote, reversed the lower courts’ decision, effectively siding with the generic-drug manufacturers.4
Facts of the Case
Five years after the FDA approved Wyeth’s new drug application (NDA) for metoclopramide (Reglan) for use in treating digestive tract diseases, primarily reflux, generic-drug manufacturers began making and distributing a generically equivalent product with approval to do so from the FDA. Postmarketing surveillance demonstrated that long-term use of metoclopramide can cause tardive dyskinesia with severe neurologic problems. Wyeth started revising its labeled warnings to reflect this newly acquired evidence and made these changes at various times up until 2009.
Plaintiffs Gladys Mensing and Julie Demahy claimed that they had developed tardive dyskinesia after long-time use of generic metoclopramide. They sued the generic manufacturers under the applicable state product-liability laws claiming that the generic drug’s warnings were inadequate under state law. Both plaintiffs argued that the generic manufacturers should be held liable because the companies: 1) failed to warn of the serious risks associated with long-term use of the drug; 2) failed to request a labeling change revision with the FDA under the “Changes Being Effected” (CBE) provisions of the Food, Drug, and Cosmetic Act (FDCA); and 3) failed to report safety information directly to the medical community.5
In response, the defendant generic companies argued that the state’s product-liability laws were preempted by federal laws. One argument claimed it is impossible to add the warnings required by plaintiffs without violating federal law because the FDA prohibits generic companies from unilaterally adding any additional warning to the generic labeling that differs from the brand-name labeling. In addition, they argued that the plaintiffs’ claims created an impermissible conflict with, and posed an obstacle to, congressional objectives applicable to generic drug-manufacturers under the FDCA.6
Court of Appeal Decisions
The Courts of Appeals in both cases held that generic manufacturers failed to show it was impossible to add warnings regarding the risks of developing tardive dyskinesia and comply with federal law because generic manufacturers could have: 1) proposed a label change for both brand-name and generic drugs through the prior approval process; or, alternatively, 2) requested that the FDA send out a warning letter to health care professionals.7 Both Courts of Appeal rejected the notion that plaintiffs’ claims created an impermissible conflict with, and posed an obstacle to, congressional objectives applicable to generic-drug manufacturers under the FDCA.
Supreme Court Opinion
Justice Clarence Thomas, writing the majority opinion, held that federal drug regulations applicable to generic-drug manufacturers directly conflict with, and thus preempt, the state claims. Accordingly, the decisions of the Courts of Appeal were reversed.8 He reasoned that federal drug regulations, as interpreted by the FDA, prevented the generic manufacturers from independently changing their generic drugs’ safety labels and that the FDCA, as amended in 1984 by The Drug Price Competition and Patent Term Restoration Act (also known as the Hatch-Waxman Act),9 allows a generic-drug manufacturer to gain FDA approval simply by showing that its drug is equivalent to an already-approved brand-name drug, and that the safety and efficacy labeling proposed for its drug is the same as that approved for the brand-name drug by obtaining an abbreviated new drug application (ANDA) from the FDA.10
Giving great deference to the FDA’s own interpretation of the law and its regulations, the majority opinion denied the plaintiffs’ position that federal law nevertheless provides avenues through which the generic manufacturers could have altered their metoclopramide labels in time to prevent the injuries here. These include: 1) the FDA’s CBE process, which permits drug manufacturers, without preapproval, to add or strengthen a warning label11; and 2) sending “Dear Doctor” letters providing additional warnings to prescribing physicians and other health care professionals.12 In particular, Justice Thomas adopted the arguments that the FDA advanced in an amicus curiae brief filed in this case. The FDA denied that the generic manufacturers could have used either of these processes to unilaterally strengthen their warning labels. Justice Thomas wrote: “Where state and federal law directly conflict, state law must give way.”13 He added that:
The Court finds impossibility here. If the [generic] manufacturers had independently changed their labels to satisfy their state-law duty to attach a safer label to their generic metoclopramide, they would have violated the federal requirement that generic drug labels be the same as the corresponding brand-name drug labels. Thus, it was impossible for them to comply with both state and federal law. And even if they had fulfilled their federal duty to ask for FDA help in strengthening the corresponding brand-name label, assuming such a duty exists, they would not have satisfied their state tort-law duty. State law demanded a safer label; it did not require communication with the FDA about the possibility of a safer label.
Here, it is enough to hold that when a party cannot satisfy its state duties without the Federal Government’s special permission and assistance, which is dependent on the exercise of judgment by a federal agency, that party cannot independently satisfy those state duties for preemption purposes.14
Most interesting, if not unexpected, the majority opinion distinguishes a prior case, Wyeth v. Levine,15,16 where the Court held that federal regulatory approval of a medication does not shield the manufacturer from liability under state law. At first blush, it would seem that the Wyeth case would have favored the plaintiffs state law claims for product-liability lawsuits. Putting the Wyeth decision into perspective, Justice Thomas said that the case “held that a state tort action against a brand-name drug manufacturer for failure to provide an adequate warning label was not preempted because it was possible for the manufacturer to comply with both state and federal law under the FDA’s CBE regulation.”17 Getting to the crux of the matter, Justice Thomas stated:
The federal statutes and regulations that apply to brand-name drug manufacturers differ, by Congress’ design, from those applicable to generic drug manufacturers. And different federal statutes and regulations may, as here, lead to different preemption results. This Court will not distort the Supremacy Clause in order to create similar preemption across a dissimilar statutory scheme. Congress and the FDA retain authority to change the law and regulations if they so desire.18
The four Justices in the minority saw the controlling laws in nearly an opposite manner. Writing for the minority, Justice Sonia Sotomayor chided the majority, stating:
The Court today invokes the doctrine of impossibility preemption to hold that federal law immunizes generic-drug manufacturers from all state-law failure-to-warn claims because they cannot unilaterally change their labels. I cannot agree. We have traditionally held defendants claiming impossibility to a demanding standard: Until today, the mere possibility of impossibility had not been enough to establish preemption.
[The Court majority] invents new principles of preemption law out of thin air to justify its dilution of the impossibility standard. It effectively rewrites our decision in Wyeth v. Levine, which holds that federal law does not preempt failure-to-warn claims against brand-name drug manufacturers. And a plurality of the Court tosses aside our repeated admonition that courts should hesitate to conclude that Congress intended to preempt state laws governing health and safety. As a result of today’s decision, whether a consumer harmed by inadequate warnings can obtain relief turns solely on the happenstance of whether her pharmacist filled her prescription with a brand-name or generic drug. The Court gets one thing right: This outcome “makes little sense.”19
Importantly, Justice Sotomayor noted that this decision affects 75% of all prescription drugs dispensed in the U.S. With a bit of stinging sarcasm, she stated that the rationale for the majority’s opinion is reductio ad absurdum (“a mode of argumentation that seeks to establish a contention by deriving an absurdity from its denial, thus arguing that a thesis must be accepted because its rejection would be untenable”).20 She read the majority opinion to say: “If the possibility of FDA approval of a label change is sufficient to avoid conflict in these cases, it warns, as a ‘logical conclusion’ so too would be the possibility that the FDA might rewrite its regulations or that Congress might amend the Hatch-Waxman Amendments.” She concluded, “The logic of this conclusion escapes me. Conflict analysis necessarily turns on existing law. It thus would be ridiculous to conclude that federal and state law do not conflict on the ground that the defendant could have asked a federal agency or Congress to change the law.”21
As a matter of logic, it is nearly incomprehensible that this case was decided on the machinations of the majority. How or why this case is distinguishable from the monumental Wyeth v. Levine case is likewise unfathomable. Brand-name manufacturers can be held liable under state product-liability laws for failure to provide adequate warnings, but generic-drug companies cannot be held liable for the same thing, simply because there may be differences in the labels of the brand versus the generic because of a bureaucratic hiccup. Irrespective of the wanting logic, we must now live with the holding as the supreme law of the land.
The point that pharmacists should take note of is that the labeling for brand-name drugs will not always be identical to the labeling on generic equivalents. This could be important in some situations, like the one described here. Because you are dispensing a generic, the warning signals popping up on your data entry system might not be the same as those that would appear if the brand-name drug were being dispensed. Pharmacists should be familiar with the rare but very real possibility of the differences in labeled warnings to make sure patient counseling is complete and accurate.
1. Vivian JC Last words: data mining is legal. US Pharm. 2011;36(8):68-74. www.uspharmacist.com/content/
2. Pliva, Inc. v. Mensing, U.S. Supreme Court No. 00-993, June 23, 2011. www.supremecourt.gov/opinions/
3. Actavis Elizabeth, LLC v. Mensing, also on certiorari to the same court, and No. 09-1501, Actavis, Inc. v. Demahy, on certiorari to the U.S. Court of Appeals for the Fifth Circuit.
4. Vivian JC. Generic manufacturer liability. US Pharm. 2010;35(8):60-63. www.uspharmacist.com/content/
5. Day KS. Supreme Court observations: PLIVA v. Mensing. The Legal Pulse. July 12, 2011. http://wlflegalpulse.com/2011/
6. See Note 3, supra.
7. In addition to submitting a supplemental application and requesting that the FDA send out warning letters to physicians, the Fifth Circuit maintained that generic manufacturers could make unilateral changes through the CBE process. See Note 3, supra.
8. 588 F3d 603 and 593 F3d 428, reversed and remanded.
9. P.L. 98-417.
10. Abbreviated new drug application (ANDA): generics. FDA. March 21, 2011. www.fda.gov/drugs/
11. Guidance for Industry. Public availability of labeling changes in “Changes Being Effected” supplements. FDA. September 18, 2006. www.fda.gov/downloads/Drugs/
12. Product safety information. Dear doctor letters. FDA. May 18, 2010. www.fda.gov/AnimalVeterinary/
13. Wyeth v. Levine, 555 U.S. 555, 583 (2009), holding that Federal regulatory approval of a medication does not shield the manufacturer from liability under state law.
14. See Note 2, supra.
15. 555 U.S. 555 (2009).
16. Vivian JC. Federal preemption of states’ drug product liability laws DOA: FDA labeling regulations are floors, not ceilings. US Pharm. 2009;34(5):50-52. www.uspharmacist.com/content/
17. Slip Op No. 06-1249, 2009 U.S. Lexis 1774, 555 U.S. (2009), at 572-573.
18. See Note 2, supra.
19. See Note 2, supra.
20. Reductio ad absurdum. Internet Encyclopedia of Philosophy. www.iep.utm.edu/reductio/. Accessed July 28, 2011. This is a site worth reading for those interested in how arguments in the law and other forms of disagreements may be formulated.
21. See Note 2, supra.
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