In a decision issued on March 4th, the United States Supreme Court dealt a serious (albeit not entirely fatal) blow to the premise that Federal law, specifically the Food and Drug Administration's approval of label warnings on a prescription pharmaceutical, pre-empts state law claims for failure to adequately warn of risks associated with the use of a drug. In the case of Wyeth v Levine, the Court held that Federal law did not pre-empt this plaintiff's claim that a drug label failed to adequately warn about a serious side effect associated with a particular administration of the drug. The Court noted, however, that it did not have to decide the broader issue of whether a state rule in direct conflict with a federal labeling mandate is pre-empted.
The plaintiff, Diane Levine, had been treated with Phenergan, an anti-nausea drug manufactured and marketed by Wyeth for over 50 years. Levine received the drug intravenously, as authorized by the product label. Unfortunately, the drug somehow entered Ms. Levine's artery, resulting in gangrene and the eventual amputation of Ms. Levine's forearm. The product label carried a rather comprehensive warning about the risk of arterial exposure, urged caution when administering the drug, and described the serious consequences of such exposure, including the potential for gangrene and amputation. Ms. Levine took the position, however, that, because some similar adverse experiences involving the same method of intravenous administration had been reported to Wyeth over the years, Wyeth should have taken steps to further enhance the label warning for the drug.
Wyeth responded that it would have been impossible for it to have complied with a state-law duty to modify the Phenergan label without violating Federal labeling requirements. Wyeth argued that FDA had approved the label language and that any subsequent changes could be made only after FDA's approval. The Court disagreed. It reiterated its own long-held position that the manufacturer, not FDA, bears the primary responsibility for drug labeling, because manufacturers have "superior access to information." The Court also indicated that the FDA regulations provide mechanisms for a manufacturer to add safety information in drug labels, including one mechanism that allows safety information to be added even in advance of FDA approval. The Court acknowledged that FDA has the ultimate authority to reject any labeling changes made in advance of its approval, but pointed to the absence of any clear evidence that FDA would not have approved enhanced warnings in the Phenergan label. Relying on what appears to be a rather passive regulatory history on the specific warning in question, the Court could not conclude that it would have been impossible for Wyeth to comply with both state and federal law requirements.
The Court also rejected as "an overly broad interpretation" Wyeth's argument that altering the label could have exposed Wyeth to liability for misbranding or unauthorized distribution. Instead, the Court stated that the manufacturer "is charged both with crafting an adequate label and with ensuring that its warnings remain adequate as long as the drug is on the market." The Court concluded that, once Wyeth became aware of the risk associated with the method of administration, Wyeth had a state law duty to warn of the risk and could have done so in a manner that complied with federal law.
The Court also gave short-shrift to Wyeth's reliance on language in the preamble to the FDA's final labeling rule published in 2006 specifying the content and format of prescription drug labels. The preamble declared that FDA approval of pharmaceuticals pre-empts contrary state law. The Court noted first that if Congress believed that state lawsuits posed an obstacle to its objectives, it could have enacted an express pre-emption provision as it did in 1976 for medical devices (recently upheld by the court in Riegel v. Medtronic, Inc.), but it had not done so. The Court went on to characterize the preamble language as nothing more than "an agency's mere assertion that state law is an obstacle to achieving its statutory objectives." The Court further noted that, in proposing the drug labeling regulation in 2000, the FDA explicitly stated that the "proposed rule did not propose to pre-empt state law" and that the 2006 preamble language, therefore, represented a "sweeping" change in FDA's position without giving interested parties an opportunity to comment. The Court found the FDA's views on state law in the preamble "inherently suspect" and determined that the preamble was inconsistent with both Congressional purposes and the FDA's longstanding past posture.
While the long term impact of this decision will take time to unfold, some initial impressions include:
- Preemption in the pharmaceutical world has been seriously limited, but not eliminated.
- Preemption cases will be much more difficult.
- Such cases will be fact intensive with an emphasis on the degree of involvement of FDA in the specific warnings being challenged.
- It will be an uphill battle — but not impossible — to win on preemption.
- On the medical device front, Riegel remains good law. In fact, the court cites Riegel with approval several times. HOWEVER, because the Levine decision may increase the pressure on Congress to reverse Riegel, the medical device industry must be prepared to vigorously support Riegel.
- The next major test will come quickly when the Supreme Court decides whether to hear the Colacicco case, in which the Third Circuit found preemption on a better regulatory history than in Levine. Hopefully, the court will let Colacicco stand.
- The manufacturer, not FDA, is responsible for the content of product labeling. The Supreme Court made it clear that industry cannot simply "pass the buck" to FDA.
- Manufacturers must engage in regular, diligent review of all product labeling and warnings, particularly in light of reported adverse events. In Levine, the drug was on the market for nearly 50 years, and the product label had been updated approximately once a decade. The Supreme Court's message is that this was not enough.
- To improve the prospects for a pre-emption defense to succeed, regulatory and product liability counsel need to be involved not only in developing the product and regulatory strategy at the earliest stages of label development, but also in assessment of reported adverse events. Also, maintaining a solid record of FDA's engagement in label development is critical if a claim of pre-emption is to succeed.