Practice Tip: Undoing Pliva Inc. v. Mensing

With Justice Thomas's words seemingly in mind, several U.S. Senators introduced the Patient Safety and Generic Labeling Improvement Act (S. 2295, 112th Cong. (2d Sess. 2012)), a bill seeking to undo Pliva and hold generic drug manufacturers to the same labeling obligations as their brand-name counterparts. This article examines the relationship between Pliva and the Patient Safety and Generic Labeling Improvement Act and discusses the potential ramifications for generic drug manufacturers should the Act be signed into law.

Pliva, Inc. v. Mensing

Pliva is a relatively typical failure-to-warn case of the sort routinely brought against drug manufacturers. Pliva, Inc. (Pliva) and other drug manufacturers produced the generic version of brand-name prescription drug Reglan, commonly used to treat digestive tract problems like diabetic gastroparesis and gastroesophageal reflux disorder. Id. at 2572. Plaintiffs, consumers of the generic drug metroclopramide, brought suit under state tort laws alleging that, despite mounting scientific evidence, the generic drug manufacturers failed to warn consumers adequately that use of metroclopramide carries an increased risk of the neurological disorder tardive dyskinesia. Id. at 2573.

Citing 21 U.S.C. ' 355(j)(2)(A)(v) and its corresponding federal regulations, the generic drug's manufacturer sought to have the consumers' state law tort claims dismissed, arguing that the claims were preempted by federal regulations that required generic drug manufacturers to use the same safety and efficacy labeling as their brand name counterparts. Accordingly, the generic drug manufacturer argued that it was impossible to comply simultaneously with both federal law and any state law duty that required it to use a different label from a brand-name counterpart. Id. at 2573.

Under the Food, Drug, and Cosmetic Act (FDCA), a brand-name drug manufacturer seeking initial federal approval to market a drug must demonstrate to the FDA that the new drug is safe and effective, and that the proposed label for the drug is accurate and adequately warns consumers of the risks associated with taking the drug. Pliva, 131 S.Ct. at 2574 (citing 21 U.S.C. ' 301 et seq.). Generic drug manufacturers, however, are not held to the same requirements. Instead, relying on the fact that a brand-name drug manufacturer already has demonstrated safety, efficacy, and adequate labeling, generic drug manufacturers can gain FDA approval to market a generic drug by showing that its safety and efficacy labeling is the same as the labeling approved for the brand-name drug. Id. at 2574. As the Supreme Court noted, the result of this regulatory scheme is that “brand-name and generic drug manufacturers have different federal labeling duties. A brand-name manufacturer seeking new drug approval is responsible for the accuracy and adequacy of its label. ' A manufacturer seeking generic drug approval, on the other hand, is responsible for ensuring that its warning label is the same as the brand name's.” Id.

In Pliva, plaintiffs argued that this regulatory scheme did not preclude generic drug manufacturers from deviating from the brand-name drug manufacturer's warning label to provide stronger warnings after initial FDA approval. Id. at 2575. Specifically, plaintiffs argued that generic drug manufacturers could comply with federal law and state law requirements that sought stronger warning labels by initially demonstrating to the FDA that the generic drug's warning label was the same as the brand name counterpart and, after approval, providing a stronger warning label that provided additional warnings in light of prevailing scientific evidence. Id. The Supreme Court rejected plaintiffs' arguments, holding that generic drug manufacturer labels are required to be the same as the brand-name labels and that any state law claims that sought to require a generic drug manufacturer to use a different label are preempted. Id. at 2578. The Supreme Court explained:

If the Manufacturers had independently changed their labels to satisfy their state-law duty, they would have violated federal law. Taking [Plaintiffs'] allegations as true, state law imposed on the Manufacturers a duty to attach a safer label to their generic metoclopramide. Federal law, however, demanded that generic drug labels be the same at all times as the corresponding brand-name drug labels. Thus it was impossible for the Manufacturers to comply with both their state-law duty to change the label and their federal law duty to keep the label the same.

Id.

This holding effectively created a dual standard for drug labeling, a standard in which brand name manufacturers can be held liable for failing to adequately warn consumers about dangerous health effects, but generic drug manufacturers are shielded from tort liability. The practical effect of the holding in Pliva was not lost on the Supreme Court: “We recognize that from the perspective of [plaintiffs], finding preemption here but not in Wyeth makes little sense. Had [plaintiffs] taken Reglan, the brand-name prescribed by their doctors, Wyeth would control and their lawsuits would not be preempted. But because pharmacists, acting in full accord with state law, substituted generic metoclopramide instead, federal law preempts these lawsuits.” Id. at 2581. But the practical implications did not alter the Supreme Court's analysis: “[I]t is not the Court's task to decide whether the statutory scheme established by Congress is unusual or even bizarre.” Id. at 2582.

With this in mind the Supreme Court's majority opinion concluded:

It is beyond dispute that the federal statutes and regulations that apply to brand-name drug manufacturers are meaningfully different than those that apply to generic drug manufacturers. Indeed, it is the special, and different, regulation of generic drugs that allowed the generic drug to expand, bringing more drugs more quickly and cheaply
to the public. But different federal statutes and regulations may, as here, lead to different preemption results. We will not distort the Supremacy Clause in order to create similar pre-emption across a dissimilar statutory scheme. As always, Congress and the FDA retain the authority to change the law and regulations as they so desire.

Id. (emphasis added).

Patient Safety and Generic Labeling Improvement Act

Seemingly responding to the Supreme Court's invitation, several Senators introduced the Patient Safety and Generic Labeling Improvement Act. While the text of the bill is quite short, the preamble to the bill describes its purpose: “[t]o permit manufacturers of generic drugs to provide additional warnings with respect to such drugs in the same manner that the Food and Drug Administration allows brand names to do so.” Id. In relevant part, the bill seeks to amend the FDCA and provides that the holder of an approved generic drug application may change the labeling of a drug so approved in the same manner authorized by regulation of the holder of an approved new drug. Id. Additionally, the bill provides that in the event a labeling change is made by a generic drug manufacturer, the Secretary of Health and Human Services may order conforming changes to the labeling of the equivalent listed drug and any other drug that corresponds to such listed drug. Id.

The bill has significant support behind it. In May 2012, the National Association of Attorneys General authored a letter, signed by Attorneys General in 41 states, urging Congress to pass the Patient Safety and Generic Labeling Improvement Act. The Attorneys General letter asserts that the preemption holding in Pliva produces arbitrary and unfair results in that “[c]onsumers whose prescriptions happen to be filled with the brand-name version of a drug are protected by state law from inadequate warnings, but consumers whose pharmacists fill their prescriptions with the generic version are now denied this protection” and that “[t]he adverse consequences are magnified by the fact that over 70% of prescriptions in the United States are filled with generic drugs.” Id. The Attorneys General letter concludes that “[f]ortunately, as the Supreme Court made clear in PLIVA [sic], Congress can readily cure this problem by amending federal law. Congress should do so, to restore for consumers of generic drugs the same protections that exist for consumers of brand-name drugs.” Id.

Implications for Generic Drug Manufacturers

Should the Patient Safety and Generic Labeling Improvement Act be enacted into law, the Act would have profound implications for generic drug manufacturers. Because generic drug manufacturers would no longer be shielded from state law failure-to-warn claims under the doctrine of preemption, these manufacturers would be held to the same post-approval labeling requirements that currently apply to brand-name drug manufacturers. Accordingly, the Supreme Court's decision in Wyeth v. Levine, 555 U.S. 555 (2009), is instructive in that it provides insight as to the regulations and laws that would govern generic drug manufacturers when preemption no longer applies.

In Wyeth, the plaintiff alleged that the manufacturer of Phenergan, a brand-name drug, failed to provide an adequate warning label because it did not warn that directly injecting the drug into a patient's veins creates a significant risk of gangrene. Id. at 558. While a drug manufacturer is generally permitted to make changes to a drug label only after the FDA approves a supplemental application, the Supreme Court rejected Wyeth's preemption arguments by holding that brand-name drug manufacturers are permitted to change a drug's label without the FDA pre-approving the labeling change under certain circumstances. Id. at 568. Specifically, the Court explained that the changes-being-effected process provides that if a brand-name drug manufacturer is changing a drug label to add or strengthen a contraindication, warning, precaution, or adverse reaction to or to add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the product, the drug manufacturer may make the labeling change without waiting for FDA approval. Id. (citing 21 CFR ” 341.70(c)(6)(iii)(A), (C)).

With this in mind, the Court explained that the FDCA and its regulatory framework provide that a drug manufacturer is ultimately responsible for its label and that it explicitly provides a mechanism for adding safety information to the label prior to FDA approval. Id. at 570.

If the Patient Safety and Generic Labeling Improvement Act becomes law, generic drug manufacturers will be held to the same labeling standards as brand name manufacturers. Under the Court's analysis in Wyeth, this presumably would mean that generic drug manufacturers can no longer rely on the simple fact that their label mirrors that of their brand-name equivalent. Instead, generic drug manufacturers will be under a duty to ensure that that their drug labels adequately warn consumers of potential harms associated with taking the drug and could be under a duty to make changes to their labels to reflect newly acquired information regarding potential risks.

Conclusion

Certain members of congress have apparently answered Justice Thomas's invitation to change the current preemption standard created by the Supreme Court in Pliva as applied to generic drug manufacturer labeling requirement. While it is not clear whether the Patient Safety and Generic Labeling Improvement Act ultimately will be enacted, generic drug manufacturers should proactively take into consideration the implications and new affirmative responsibilities the Act will create if enacted. Such a change to the current regulatory scheme could require generic drug manufacturers to invest significant time and resources to ensure that their drugs' labels are adequate and that all necessary precautions have been taken to avoid unwanted litigation based on the generic drug manufacturers' alleged failure to warn of the potential health risks associated with using their generic drugs.

Josh Becker, a member of this newsletter's Board of Editors, is a partner and Travis Thompson is an associate at Alston & Bird LLP, resident in the Atlanta office. Both focus their practices on product liability, mass tort, and class action defense

Congress is discussing taking away generic drug manufacturers' labeling litigation shield.

Introduction

“As always, Congress and the FDA retain the authority to change the law and the regulations if they so desire.” Pliva, Inc. v. Mensing , 131 S.Ct. 2567, 2581 (2011). These were the final words of Justice Thomas's majority opinion in a Supreme Court decision effectively shielding manufacturers of generic drugs from state law tort claims alleging harm resulting from inadequate drug labeling. Criticism of Pliva has been widespread in some circles, with the critics arguing that Pliva's holding creates a double standard in which brand-name prescription drug manufacturers can be held liable for inadequate drug labeling, but claims against generic drug manufacturers are preempted by federal law.

With Justice Thomas's words seemingly in mind, several U.S. Senators introduced the Patient Safety and Generic Labeling Improvement Act (S. 2295, 112th Cong. (2d Sess. 2012)), a bill seeking to undo Pliva and hold generic drug manufacturers to the same labeling obligations as their brand-name counterparts. This article examines the relationship between Pliva and the Patient Safety and Generic Labeling Improvement Act and discusses the potential ramifications for generic drug manufacturers should the Act be signed into law.

Pliva, Inc. v. Mensing

Pliva is a relatively typical failure-to-warn case of the sort routinely brought against drug manufacturers. Pliva, Inc. (Pliva) and other drug manufacturers produced the generic version of brand-name prescription drug Reglan, commonly used to treat digestive tract problems like diabetic gastroparesis and gastroesophageal reflux disorder. Id. at 2572. Plaintiffs, consumers of the generic drug metroclopramide, brought suit under state tort laws alleging that, despite mounting scientific evidence, the generic drug manufacturers failed to warn consumers adequately that use of metroclopramide carries an increased risk of the neurological disorder tardive dyskinesia. Id. at 2573.

Citing 21 U.S.C. ' 355(j)(2)(A)(v) and its corresponding federal regulations, the generic drug's manufacturer sought to have the consumers' state law tort claims dismissed, arguing that the claims were preempted by federal regulations that required generic drug manufacturers to use the same safety and efficacy labeling as their brand name counterparts. Accordingly, the generic drug manufacturer argued that it was impossible to comply simultaneously with both federal law and any state law duty that required it to use a different label from a brand-name counterpart. Id. at 2573.

Under the Food, Drug, and Cosmetic Act (FDCA), a brand-name drug manufacturer seeking initial federal approval to market a drug must demonstrate to the FDA that the new drug is safe and effective, and that the proposed label for the drug is accurate and adequately warns consumers of the risks associated with taking the drug. Pliva, 131 S.Ct. at 2574 (citing 21 U.S.C. ' 301 et seq.). Generic drug manufacturers, however, are not held to the same requirements. Instead, relying on the fact that a brand-name drug manufacturer already has demonstrated safety, efficacy, and adequate labeling, generic drug manufacturers can gain FDA approval to market a generic drug by showing that its safety and efficacy labeling is the same as the labeling approved for the brand-name drug. Id. at 2574. As the Supreme Court noted, the result of this regulatory scheme is that “brand-name and generic drug manufacturers have different federal labeling duties. A brand-name manufacturer seeking new drug approval is responsible for the accuracy and adequacy of its label. ' A manufacturer seeking generic drug approval, on the other hand, is responsible for ensuring that its warning label is the same as the brand name's.” Id.

In Pliva, plaintiffs argued that this regulatory scheme did not preclude generic drug manufacturers from deviating from the brand-name drug manufacturer's warning label to provide stronger warnings after initial FDA approval. Id. at 2575. Specifically, plaintiffs argued that generic drug manufacturers could comply with federal law and state law requirements that sought stronger warning labels by initially demonstrating to the FDA that the generic drug's warning label was the same as the brand name counterpart and, after approval, providing a stronger warning label that provided additional warnings in light of prevailing scientific evidence. Id. The Supreme Court rejected plaintiffs' arguments, holding that generic drug manufacturer labels are required to be the same as the brand-name labels and that any state law claims that sought to require a generic drug manufacturer to use a different label are preempted. Id. at 2578. The Supreme Court explained:

If the Manufacturers had independently changed their labels to satisfy their state-law duty, they would have violated federal law. Taking [Plaintiffs'] allegations as true, state law imposed on the Manufacturers a duty to attach a safer label to their generic metoclopramide. Federal law, however, demanded that generic drug labels be the same at all times as the corresponding brand-name drug labels. Thus it was impossible for the Manufacturers to comply with both their state-law duty to change the label and their federal law duty to keep the label the same.

Id.

This holding effectively created a dual standard for drug labeling, a standard in which brand name manufacturers can be held liable for failing to adequately warn consumers about dangerous health effects, but generic drug manufacturers are shielded from tort liability. The practical effect of the holding in Pliva was not lost on the Supreme Court: “We recognize that from the perspective of [plaintiffs], finding preemption here but not in Wyeth makes little sense. Had [plaintiffs] taken Reglan, the brand-name prescribed by their doctors, Wyeth would control and their lawsuits would not be preempted. But because pharmacists, acting in full accord with state law, substituted generic metoclopramide instead, federal law preempts these lawsuits.” Id. at 2581. But the practical implications did not alter the Supreme Court's analysis: “[I]t is not the Court's task to decide whether the statutory scheme established by Congress is unusual or even bizarre.” Id. at 2582.

With this in mind the Supreme Court's majority opinion concluded:

It is beyond dispute that the federal statutes and regulations that apply to brand-name drug manufacturers are meaningfully different than those that apply to generic drug manufacturers. Indeed, it is the special, and different, regulation of generic drugs that allowed the generic drug to expand, bringing more drugs more quickly and cheaply
to the public. But different federal statutes and regulations may, as here, lead to different preemption results. We will not distort the Supremacy Clause in order to create similar pre-emption across a dissimilar statutory scheme. As always, Congress and the FDA retain the authority to change the law and regulations as they so desire.

Id. (emphasis added).

Patient Safety and Generic Labeling Improvement Act

Seemingly responding to the Supreme Court's invitation, several Senators introduced the Patient Safety and Generic Labeling Improvement Act. While the text of the bill is quite short, the preamble to the bill describes its purpose: “[t]o permit manufacturers of generic drugs to provide additional warnings with respect to such drugs in the same manner that the Food and Drug Administration allows brand names to do so.” Id. In relevant part, the bill seeks to amend the FDCA and provides that the holder of an approved generic drug application may change the labeling of a drug so approved in the same manner authorized by regulation of the holder of an approved new drug. Id. Additionally, the bill provides that in the event a labeling change is made by a generic drug manufacturer, the Secretary of Health and Human Services may order conforming changes to the labeling of the equivalent listed drug and any other drug that corresponds to such listed drug. Id.

The bill has significant support behind it. In May 2012, the National Association of Attorneys General authored a letter, signed by Attorneys General in 41 states, urging Congress to pass the Patient Safety and Generic Labeling Improvement Act. The Attorneys General letter asserts that the preemption holding in Pliva produces arbitrary and unfair results in that “[c]onsumers whose prescriptions happen to be filled with the brand-name version of a drug are protected by state law from inadequate warnings, but consumers whose pharmacists fill their prescriptions with the generic version are now denied this protection” and that “[t]he adverse consequences are magnified by the fact that over 70% of prescriptions in the United States are filled with generic drugs.” Id. The Attorneys General letter concludes that “[f]ortunately, as the Supreme Court made clear in PLIVA [sic], Congress can readily cure this problem by amending federal law. Congress should do so, to restore for consumers of generic drugs the same protections that exist for consumers of brand-name drugs.” Id.

Implications for Generic Drug Manufacturers

Should the Patient Safety and Generic Labeling Improvement Act be enacted into law, the Act would have profound implications for generic drug manufacturers. Because generic drug manufacturers would no longer be shielded from state law failure-to-warn claims under the doctrine of preemption, these manufacturers would be held to the same post-approval labeling requirements that currently apply to brand-name drug manufacturers. Accordingly, the Supreme Court's decision in Wyeth v. Levine , 555 U.S. 555 (2009), is instructive in that it provides insight as to the regulations and laws that would govern generic drug manufacturers when preemption no longer applies.

In Wyeth, the plaintiff alleged that the manufacturer of Phenergan, a brand-name drug, failed to provide an adequate warning label because it did not warn that directly injecting the drug into a patient's veins creates a significant risk of gangrene. Id. at 558. While a drug manufacturer is generally permitted to make changes to a drug label only after the FDA approves a supplemental application, the Supreme Court rejected Wyeth's preemption arguments by holding that brand-name drug manufacturers are permitted to change a drug's label without the FDA pre-approving the labeling change under certain circumstances. Id. at 568. Specifically, the Court explained that the changes-being-effected process provides that if a brand-name drug manufacturer is changing a drug label to add or strengthen a contraindication, warning, precaution, or adverse reaction to or to add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the product, the drug manufacturer may make the labeling change without waiting for FDA approval. Id. (citing 21 CFR ” 341.70(c)(6)(iii)(A), (C)).

With this in mind, the Court explained that the FDCA and its regulatory framework provide that a drug manufacturer is ultimately responsible for its label and that it explicitly provides a mechanism for adding safety information to the label prior to FDA approval. Id. at 570.

If the Patient Safety and Generic Labeling Improvement Act becomes law, generic drug manufacturers will be held to the same labeling standards as brand name manufacturers. Under the Court's analysis in Wyeth, this presumably would mean that generic drug manufacturers can no longer rely on the simple fact that their label mirrors that of their brand-name equivalent. Instead, generic drug manufacturers will be under a duty to ensure that that their drug labels adequately warn consumers of potential harms associated with taking the drug and could be under a duty to make changes to their labels to reflect newly acquired information regarding potential risks.

Conclusion

Certain members of congress have apparently answered Justice Thomas's invitation to change the current preemption standard created by the Supreme Court in Pliva as applied to generic drug manufacturer labeling requirement. While it is not clear whether the Patient Safety and Generic Labeling Improvement Act ultimately will be enacted, generic drug manufacturers should proactively take into consideration the implications and new affirmative responsibilities the Act will create if enacted. Such a change to the current regulatory scheme could require generic drug manufacturers to invest significant time and resources to ensure that their drugs' labels are adequate and that all necessary precautions have been taken to avoid unwanted litigation based on the generic drug manufacturers' alleged failure to warn of the potential health risks associated with using their generic drugs.

Josh Becker, a member of this newsletter's Board of Editors, is a partner and Travis Thompson is an associate at Alston & Bird LLP, resident in the Atlanta office. Both focus their practices on product liability, mass tort, and class action defense