FDA Pre-emption Wins On Appeal, But Coming Supreme Court Case May Mean More For Drug Liability Risks

Third Circuit Court of Appeals tosses failure-to-warn claims against GSK and Pfizer.

Lawsuits brought against GlaxoSmithKline and Pfizer over "failure to warn" claims for their antidepressant drugs are pre-empted by FDA's authority over labeling, the Third Circuit U.S. Court of Appeals has ruled.

In December, the appeals court heard arguments in the consolidated cases Colacicco v. Apotex and McNellis v. Pfizer. In Colacicco the plaintiff claims Apotex and GSK failed to adequately warn of suicide risk on labeling for generic and brand name Paxil (paroxetine), and in McNellis the plaintiff makes similar claims about Zoloft (sertraline) labeling.

District courts issued opposite rulings on pre-emption in these cases. In Colacicco, a Pennsylvania district court found that federal regulations pre-empt state tort law where imposing state tort liability for failure to warn would conflict with FDA-approved labeling. But in McNellis, a New Jersey district court ruled that federal labeling requirements are minimum standards and that states can impose stricter requirements for labeling and warnings through tort law.

On April 8, the court of appeals ruled that pre-emption applied in both cases.

"Because the standard for adding a warning to drug labeling is the existence of 'reasonable evidence of an association of a serious hazard with a drug,' [federal statute] authorizes the FDA to prohibit false or misleading labeling, a state-law obligation to include a warning asserting the existence of an association between SSRIs and suicidality directly conflicts with the FDA's oft-repeated conclusion that the evidence did not support such an association," wrote circuit judge Delores Sloviter.

"Therefore, under the circumstances of this case, the plaintiffs' failure-to-warn claims are pre-empted by the FDA's actions taken in accordance with its statutory authority," she wrote.

"The court got it exactly right, under the facts presented and the regulatory history of these two medications, and the timing of these events, that it simply would make no sense not to hold these claims pre-empted," said Malcolm Wheeler, partner at Wheeler, Trigg & Kennedy, which represented Pfizer.

Sol Weiss, attorney for the McNellis case, on the other hand, said he was "very disappointed" with the judge's decision and that they are planning on asking for a review from the third circuit.

The appeals court ruling follows a similar case, Warner-Lambert v. Kent, in which the Supreme Court justices deadlocked in March ¹ (Also see "Supreme Court Reaches Tie Vote in FDA Preemption Case" - Pink Sheet, 3 Mar, 2008.).

At issue in that case was whether federal law pre-empts a Michigan statute that allows someone to bring a product liability suit only if the manufacturer concealed information from the FDA. Michigan residents claim that Warner-Lambert concealed safety and efficacy information from FDA that would have prevented the diabetes drug Rezulin (troglitazone) from being approved or led to its removal from the market prior to 2000.

Since there was no majority ruling, no precedent arose from the decision.

But this appeals court ruling may have bearing on a coming Supreme Court case, Wyeth v. Levine, which involves a similar dispute over what constitutes an adequate label warning ² (Also see "Firms May Revise Labeling Without FDA Okay Only When New Safety Data Emerges" - Pink Sheet, 15 Jan, 2008.).

The plaintiff in the case received an intravenous injection of Phenergan (promethazine) directly into her arm, an administration referred to as IV-push. The drug inadvertently went into an artery, causing gangrene that ultimately resulted in amputation of the plaintiff's hand and forearm. The plaintiff sued Wyeth, claiming the label should not have allowed IV-push as a means of administering the drug.

Wyeth argued FDA was aware of the dangers of IV-push administration and instructed the company to use the warning on the label, which stated that "under no circumstances should Phenergan Injection be given by intra-arterial injection due to the likelihood of severe arteriospasm and the possibility of subsequent gangrene."

But a trial court rejected Wyeth's pre-emption defense and a jury awarded the plaintiff $6.7 million. The Vermont Supreme Court affirmed the decision, finding that the law allows manufacturers to avoid state failure-to-warn claims without violating federal law by making unilateral changes to FDA-approved labeling. The U.S. Solicitor General, however, asserted that FDA regulation does not allow manufacturers to make unilateral label changes based on information that was previously available to the agency.

The case is scheduled to be heard in the court term starting in October.

The Third Circuit's decision included a dissent from judge Thomas Ambro, who expressed concern that the contrary conclusions for GSK and Pfizer from the two district courts highlight the difficulty of state-federal relations. "Without a clear statement from Congress of clear evidence that state law stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress ... I am reluctant to say that the defendants' claim of a conflict has scaled the presumption against pre-emption," he wrote.

"I believe courts should fear to tread where Congress has not given us a clear statement," Ambro wrote. "Because I see sound legal and policy reasons to hold that the presumption against pre-emption is not overcome, I would allow the plaintiffs' suits to go forward."

Bert Rein, a partner at Wiley Rein who represented the Pharmaceutical Research and Manufacturers of America in its amicus brief in support of Warner-Lambert, commented that because Colacicco was a court of appeals decision, it in no way binds the Supreme Court. But, the justices could be interested in seeing how a lower court ruled in this situation, he said.

"They've always said no court of appeals has ever sustained a pre-emption finding. Well now one has. So, it's an ice breaker in one sense."

-Lauren Smith ([email protected])