Wyeth v. Levine: The Intersection of FDA Drug Labeling Requirements, State Tort Laws, and Drug Manufacturer Responsibility According to the U.S. Supreme Court
Although it originated as a personal injury lawsuit in Vermont state court, the Wyeth v. Levine case quickly assumed the “mantel” of a constitutional law case because it involved constitutional law principles involving the doctrine of pre-emption. Under the pre-emption doctrine, federal law, including federal statutes, treaties, administrative rules, and common law “trumps” state law that is inconsistent with the specific terms of overall objectives of the federal law.
In Wyeth v. Levine, 555 U.S. (2009) (complete citation not available as of the date of this post; citations are for Slip Opinion), the Plaintiff, a professional musician, lost her hand to gangrene when she was administered Phenergan, an FDA-approved drug manufactured by Wyeth Pharmaceuticals for treating the nausea which often accompanies severe migraine headaches. During her first visit to the clinic, Phenergan was administered by an intra-muscular injection. The Plaintiff returned later in the day, but this time the drug was administered by an “IV-push” intravenous injection by the attending physician’s assistant. Unfortunately for the Plaintiff, the “second” injection procedure caused the drug to come into contact with arterial blood, resulting in the onset of gangrene and eventually the amputation of her hand and forearm.
The Plaintiff sued Wyeth in Vermont State Court on grounds of negligence for failure to provide an adequate warning concerning the potential danger of an “IV-push” procedure for administering the drug and product liability. A Vermont jury agreed and found Wyeth liable on grounds of negligence and product liability, and awarded Ms. Levine over $6,000,000.00 in damages.
Wyeth appealed the verdict to Vermont’s Supreme Court arguing that the drug’s label, which had been approved by the FDA, was in compliance with federal laws and regulations which govern drug safety and labeling requirements. Hence, the FDA’s regulatory requirements for prescription drug labels should pre-empt Vermont’s tort law which were in conflict with the FDA’s requirements. The Vermont Supreme Court affirmed the verdict and rejected Wyeth’s position. Wyeth appealed the decision to the U.S. Supreme Court.
The issue before the U.S. Supreme Court was whether Phenergan’s FDA- approved warning label "preempt state law product liability claims premised on the theory that different labeling judgments were neessary to make drugs reasonably safe for use." Slip Op. at 6. According to the U.S. Supreme Court, the answer is no. The Court, in a 6 to 3 decision, to the surprise of many observers, has affirmed the Vermont Supreme Court by holding that Vermont’s tort law was not pre-empted by the FDA’s labeling requirements for Phenergan.
Justice Stevens delivered the opinion of the Court, with Justice Kennedy and Justice Thomas concurring in separate opinions.
To better understand the US Supreme Court’s “pre-emption discussion,” some background on the pre-emption doctrine may be helpful. Generally pre-emption can be broken down into three distinct types: Conflict Pre-emption, Field Pre-emption, and Implied Pre-emption. The Wyeth decision focused on Conflict Pre-emption. Under case law developed for Conflict Preemption, federal law generally will trump state law under the following two circumstances:
1. A conflict between federal and state law makes it physically impossible to comply with both federal and state standards. Florida Lime & Avocado Growers, Inc. v. Paul, 373 U.S. 132, 142-143 (1963).
2. A state law may conflict with federal law by creating an “obstacle to the accomplishment and execution of the full purposes and objectives of Congress.” Hines v. Davidowitz, 312 U.S. 52, 67 (1941).
Wyeth argued that FDA labeling requirements preempted or “trumped” Vermont’s tort laws on the basis of both types of Conflict Preemption as follows:
1. It is impossible for Wyeth to comply with both the state-law duties and federal-labeling regulations, since the latter forbids it from changing its label without FDA approval. See Fidelity Fed. Sav. & Loan Assn. v. De la Cuesta, 458 U. S. 141, 153 (1982). Slip Op. at 6.
2. Permitting states to require stronger warnings creates an unacceptable “obstacle to the accomplishment and execution of the full purposes and objectives of Congress,” Hines v. Davidowitz, 312 U. S. 52, 67 (1941), because it substitutes a lay jury’s decision about drug labeling for the expert judgment that Congress sought to entrust with drug labeling decisions when it created the FDA. Slip Op. at 6-7.
The majority’s analysis of the pre-emption issue begins by stating that “[o]ur answer to that question must be guided by two cornerstones of our pre-emption jurisprudence. “ ‘First, the purpose of Congress is the ultimate touchstone in every pre-emption case.’ ” Slip Op. at 8. citing Medtronic, Inc. v. Lohr, 518 U.S. 470, 485 (1996) (internal quotation marks omitted).
" Second, “ ‘[i]n all pre-emption cases, and particularly in those in which Congress has "legislated. . .in a field which the States have traditionally occupied, . . . we ‘start with the assumption that the historic police powers of the States were not to be superseded by the Federal Act unless that was the clear and manifest purpose of Congress.’ " Lohr, 518 U.S., at 485 (quoting Rice v. Santa Fe Elevator Corp., 331 U.S. 218 230 (1947)" Slip Op. at 8.
In reaching its conclusion that Wyeth’s two-pronged preemption argument must fail, the High Court first reviewed the history behind Congress’ establishment of the Food and Drug Administration in 1906 to the gradual expansion of the FDA’s power to ensure the safety and efficacy of prescription drugs in 1962. Since 1962, any prescription drug sold in the US must be pre-approved by the FDA before it can actually be sold in this country. Pre-market approval involves the submission of considerable safety and efficacy data to the FDA for evaluation. Clinical trials, performed according to defined clinical trial protocols are required and the results become part of the FDA “new drug” evaluation package. Slip Op. at 9-10.
Regarding Wyeth’s first pre-emption argument, the majority emphasized that re-labeling the drug to conform to Vermont law would not necessarily have violated federal labeling regulations.
Although a manufacturer generally needs FDA approval before changing a drug label, the agency's “changes being effected” (CBE) regulation permits certain unilateral labeling changes that improve drug safety without waiting for FDA approval. Such changes may include warnings that “add or strength an instruction about dosage and administration that is intended to increase the safe use of the drug product.” Slip Op. at 11 quoting the CBE regulation §§ 314.70(c)(6)(iii)(A), (C). Any such “CBE” changes must be accompanied by a supplemental application to the FDA which retains its authority to review all supplemental applications. Slip Op. at 11.
According to the majority, Wyeth’s misreading of this regulation is based on the misunderstanding that the FDA, rather than the manufacturer, bears primary responsibility for drug labeling. It is a central premise of the Food, Drug, and Cosmetic Act (FDCA) and the FDA’s regulations that the manufacturer bears responsibility for the content of its label at all times. Slip Op. at 11. Wyeth could not provide clear evidence that the FDA would not have approved a change to Phenergan’s label under the CBE regulation and therefore could not, according to the majority, prove that it was impossible for Wyeth to comply with both federal and state requirements. Slip Op. at 15.
Regarding Wyeth’s second pre-emption argument, the High Court found that Wyeth was incorrect that permitting states to require stronger warnings would interfere with Congress’ purpose of entrusting an expert agency with drug labeling decisions, because it was not Congress's intent, in writing the Food, Drug, and Cosmetic Act, to preempt state-law failure to warn actions. Slip Op. at 17. The High Court opined that Congress never intended the FDCA Food, Drug, and Cosmetics Act to pre-empt state law failure-to-warn actions. “Congress did not provide a federal remedy for consumers harmed by unsafe or ineffective drugs in the 1938 statute or in an subsequent amendment. Evidently it determined that widely available state rights of action provided appropriate relief for injured consumers.” Slip Op. at 17.
The High Court also discussed the concept of preemption on the basis of the preamble to the FDA’s 2006 regulations which stated “state-law-failure-to-warn claims threaten the FDA’s statutorily prescribed role.” Wyeth argued that this preamble preempted state law. The Court discounted Wyeth’s assertion based on its holding in Skidmore v. Swift & Co., 323 U.S. 134 where the court held that where Congress has not authorized a federal agency to pre-empt state law directly, “[t]he weight this Court accords the agency’s explanation of state law’s impact on the federal scheme depends on its thoroughness, consistency, and persuasiveness.” Slip Op. at 20.
Relying on Skidmore, the High Court stated that the “FDA’s 2006 preamble does not merit deference.” Slip Op. at 20. The majority opined that the preamble is inherently suspect in light of the FDA’s failure to offer States or other interested parties notice or opportunity for comment on the pre-emption question. Moreover, it is at odds with the available evidence of Congress’ purposes; and it reverses the FDA’s own longstanding position that state law is a complementary form of drug regulation without providing a reasoned explanation. Slip Op. at 21.
Justice Stevens went on to carefully distinguish Geier v. American Honda Motor Co., 529 U. S. 861, the case relied on Justice Alito in the minority’s dissenting opinion, which concerned the federal agency, the department of transportation. Slip Op. at 20.
The High Court further emphasized that had Congress wished to terminate state tort claims in matters involving prescription drugs it would have done so. Noting the express pre-emption language used by Congress concerning medical devices where Congress had enacted an express or direct preemption provision for medical devices in 1976, the majority concluded that Congress’ “silence on the issue [of prescription drugs], coupled with its certain awareness of the prevalence of state tort litigation, is powerful evidence” that Congress did not intend for the FDA to be exclusively responsible for ensuring drug effectiveness and safety." Slip Op. at 18.
As an aside, medical devices include products ranging from clinical assay instrumentation and reagents to sophisticated instrumentation such as MRI (magnetic resonance instrumentation) and are regulated by the FDA. As with drugs, medical devices must be pre-approved by the FDA prior to being placed on the market, and clinical trials are generally required.
The Wyeth decision clearly emphasizes that drug manufacturers are responsible for ensuring that warning labels are up-to-date, accurate and complete. That burden has always legally existed. The FDA, as a regulatory agency, relies on the information provided to it by the very companies it regulates first to approve a new product, and then to ensure the continuing safety and efficacy of the products it regulates. If a drug manufacturer becomes aware of a complication or side effect that threatens the safety of users, it has the obligation to monitor the situation and inform the FDA.
Although drugs sold with non-FDA approved labels are illegal, the CBE regulation provides a mechanism for the drug manufacturer to effect a labeling change to protect the public while the supplemental application containing the “heightened” warnings undergoes FDA review. It would certainly seem that proactive steps to address a safety and/or efficacy problem in the field would be viewed favorably by the FDA and be consistent with Congress’ intent that the drug manufacturer is ultimately responsible for ensuring the safety and efficacy of its drugs. As the High Court stated, “[a]nd the very idea that the FDA would bring an enforcement action against a manufacturer for strengthening a warning pursuant to the CBE regulation is difficult to accept – neither Wyeth nor the United States has identified a care in which the FDA has done so.” Slip Op. at 14.
As support for its rationale, the majority also cited several reports by the “experts” which state inter alia that “[t]he FDA lacks the resources for post marketing drug safety work are inadequate and that resource limitations have hobbled the agency’s ability to improve and expand this essential component of its mission.” Slip Op. at 22 This “economic” reality was also indirectly used by the High Court to drive home the point that the FDA regulations, as they apply to prescription drugs, do not pre-empt common law tort suits in state court. Slip Op. at 22. “Failure-to-warn [state court] actions, in particular, lend force to the FDCA’s premise that manufacturers, not the FDA, bear primary responsibility for their drug labeling at all times, and manufacturers have superior access to information about their drugs, especially in the postmarketing phase as new risks emerge. State tort suits . . . provide incentive for drug manufacturers to disclose safety risks promptly.” Slip Op. at 22-23.
In light of Wyeth, drug companies should take proactive steps to reduce the possibility of lawsuits in state court where the state law requirements may require “something more” to protect consumers than the labeling previously approved by the FDA. As the Wyeth Court stated, drug companies can take advantage of the “changes being effected” (CBE) regulation which permits certain unilateral labeling changes that improve drug safety. In the Wyeth case, the potential ramifications to the patient receiving Phenergan through the IV-push method were severe. Had Wyeth used the relatively “cost-effective” CBE regulation to address this issue, the revised “heightened warning” label most likely would have been found to meet the requirements of Vermont State Law and been approved by the FDA down the road. Wyeth would have been off the hook, including being off the hook for hefty legal bills.
We hope that this blog has been informative. In a nutshell, the Wyeth case holding emphasizes that prescription drug manufacturers have the ultimate responsibility for ensuring the safety and effiicacy of their products. We would recommend that if you and/or a loved one have reason to believe that you have experienced complications related to a drug prescription, that you discuss your concerns with your doctor and also visit the FDA’s website to determine if any information is available for that drug concerning reported adverse effects. You may also wish to consult with an attorney about your potential legal rights.
