Federal drug labeling law does not preempt claims that drugmaker Pfizer Inc. should have warned that its antidepressant Zoloft can cause suicidal behavior, the U.S. District Court for the Eastern District of Texas ruled March 31, denying a defense summary judgment motion (Cartwright v. Pfizer Inc., E.D. Texas, No. 04-292, 3/31/05 ).

A federal trial court in Louisiana came to the same conclusion: State law-based warning claims in a Zoloft case may proceed, the court said, denying summary judgment to the defendants on preemption grounds. Judge Ralph E. Tyson of the Middle District of Louisiana said he would issue a written opinion at a later date (Miles v. Pfizer Inc., M.D. La., No. 03-691, 3/30/05).

The court in Texas concluded that state claims do not conflict with federal labeling requirements for prescription drugs. The federal requirements set minimum standards, the U.S. District Court for the Eastern District of Texas said. States are free to impose stricter labeling and warning requirements, as long as the warnings are not false or misleading.

The court cited Congressional and agency hearings on antidepressants and suicide, the FDA's recent directive that antidepressants carry a black box warning regarding suicidal thoughts and behavior in children and adolescents, and expert testimony linking Zoloft and other drugs in its class to suicidality. "[I]t would be inconceivable," the court concluded, "to argue that an additional warning regarding suicidality would be false or misleading."

Pfizer's arguments regarding the supposed thwarting of FDA objectives in this case are misguided, the court said. "The evidence unequivocally proves that the FDA's objective, as expressed through its regulations, demonstrate that manufacturers should provide consumers with all the safety information about their drugs as soon as the information is known, which is exactly what Texas law requires. Thus, there is no FDA objective that is being subverted or thwarted."

Other Rulings, Other Briefs.

The decisions came after courts in the Northern and Southern Districts of Texas ruled that federal law did preempt suicide warning claims in Zoloft cases. The cases, Dusek v. Pfizer Inc., S.D. Texas No. H-02-3559, 2/20/04; Needleman v. Pfizer Inc., N.D. No. 3:03-CV-3074-N, 8/6/04), are on appeal before the U.S. Court of Appeals for the Fifth Circuit (32 PSLR 904, 10/4/04). Plaintiffs' briefs are due later in April.

And the trial courts' rulings--handed down before the FDA directed manufacturers in October 2004 to add the black box warning--relied on the reasoning of an amicus brief the United States had filed in a suit in federal court in California several years earlier in Motus v. Pfizer Inc., 127 F. Supp. 2d 1085 (C.D. Cal. 2000). The Motus trial court ruled against Pfizer's summary judgment motion on preemption. The government's amicus brief, filed on appeal, argued that any warning of a causal relation between Zoloft and suicide would have "misbranded" the drug because there was no scientific support for such a warning. The U.S. Court of Appeals for the Ninth Circuit ultimately decided Motus on different grounds, never reaching the preemption issue (32 PSLR 150, 2/16/04).

The Eastern District of Texas in Cartwright rejected Pfizer's efforts to rely on the amicus brief, discrediting its reasoning in light of the recent regulatory activity. "Here, on numerous occasions, the Defendant refers to the amicus brief for support of its arguments. The main flaw in Defendant's argument now is that the Plaintiffs have produced evidence to the contrary. There is support for such a warning," the court said.

Zoloft Prescribed in 2002.

Bethany Cartwright was prescribed Zoloft by a physician's assistant in May 2002. Zoloft belongs to a class of drugs known as selective serotonin reuptake inhibitors (SSRIs). These drugs are used to treat major depressive disorder, from which Cartwright suffered, as well as other psychological conditions.

Cartwright had tried Zoloft before receiving this prescription, but was unable to use the medication consistently because of side effects. After she filled this prescription, her side effects--including emergent suicidality and worsening depression-- intensified. She killed herself on May 30, 2002.

The plaintiffs, Cartwright's estate and heirs, argued that Zoloft was a cause of her suicide. They also asserted that Pfizer knew about the association between Zoloft and suicide but failed to warn of this link. Pfizer sought summary judgment on preemption grounds.

The court observed that the Food, Drug, and Cosmetic Act controls drug approval, sale, and marketing. FDA regulations mandate the format and content of all drug labeling.

The FDA granted final approval for Zoloft on Dec. 30, 1991. After approving a drug, the agency continues to monitor its safety. In this case, the agency's ongoing study of Zoloft and other SSRIs during the decade following approval continued to find no causal relationship to suicide. "Indeed, the FDA made six more explicit determinations that Zoloft was 'safe and effective' with the FDA-required labeling," up until 2003, the court said.

"This case presents a difficult and very close question of conflict preemption," the court began. It observed that state tort claims are preempted if they "stand as an obstacle to the accomplishment and execution of the full purposes and objectives" of federal law, or if they would interfere with a method by which the federal law promotes that goal.

But the court said the federal drug labeling law merely sets minimum standards with which manufacturers must comply; they expressly do not prohibit a manufacturer from adding to or strengthening the warning. "This is consistent with Congress' primary goal in enacting the FDCA, which is to protect consumers from dangerous products," the court said.

Courts Find no Preemption.

"With little exception, courts that have considered this exact issue have concluded that state failure-to-warn claims are not preempted by the FDCA and its attendant regulations," the court observed. For example, in Caraker v. Sandoz Pharmaceuticals Corp., 172 F. Supp. 2d 1018, 29 PSLR 886 (S.D. Ill. 2001), the U.S. District Court for the Southern District of Illinois found no preemption because the manufacturer was explicitly authorized by the FDA's regulations to add or strengthen its warnings without prior FDA approval.

The U.S. Supreme Court recently clarified the application of conflict preemption in Geier v. American Honda Motor Co., 28 PSLR 464 (5/29/00). State tort law requirements would pose an obstacle to the accomplishment to a complex federal regulatory scheme because the applicable regulations set forth a specific balance regarding airbags, the Court said; additional state law requirements would upset this balance. But Geier was expressly limited to the motor vehicle safety regulations at issue, the Eastern District of Texas stressed.

Before 1965, the FDA did not view its standards regarding drug warnings as the minimum requirement, the Cartwright court noted. However, regulation changes in 1965 permit a manufacturer "[t]o add or strengthen a contraindication, warning, precaution, or adverse reaction" without prior approval by the FDA, the court said, citing 21 C.F.R. 314.70(c)(6)(iii)(A).

Moreover, the regulations require a manufacturer to issue a warning whenever there is "reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved," the court said. This same regulation requires a black box warning for drugs with side effects that may lead to death or serious injury--"the very same black box warnings that the FDA's pharmoneurological drug advisory committee (PDAC) recommended be placed on all SSRI drugs, including Zoloft, regarding suicidality in children and adolescents," the court said.

Device Cases Distinguished.

Pfizer also cited a number of federal court decisions that have found preemption. However, "Pfizer's citations are misleading" because these cases are medical device cases brought under a medical device statute that contains an express preemption clause. "Express preemption caselaw has no application to this case because there is no provision in the FDCA or its regulations regarding prescription drugs which purport to preempt state law," the court said.

The court rejected Pfizer's argument that the plaintiffs' state law claims will interfere with the FDA's objective "of ensuring that all warnings are supported by scientific evidence sufficient to demonstrate that the warnings are accurate and not misleading." Pfizer ignores the FDA's primary objective, which is to protect consumers, the court said. Clearly, the FDA recognizes its dual purpose to provide scientifically accurate information and to protect consumers, the court said, because it allows and even encourages manufacturers to be proactive when learning of new safety information related to a drug.

Likewise, the court said, Texas product liability law requires manufacturers to provide consumers (or doctors, in the case of prescription drugs) with warnings regarding reasonably foreseeable or scientifically discoverable dangers at the time the product is sold. "Thus, Texas law compliments and is parallel to the FDA's regulations regarding safety warnings and, thus, does not interfere with the objectives of the FDA," the court said.

Judge William M. Steger wrote the opinion.

The Cartwright plaintiffs are represented by Dan J. Anderson in Canton, Texas; and Robert M. Brava-Partain, Jessica R. Dart, Karen Barth Menzies, and George W Murgatroyd, III of Baum Hedlund In Los Angeles.

Pfizer was represented by Laura E. DeSantos and Jack Edward Urquhart of Beirne Maynard & Parsons in Houston, and by James E. Hooper and Amy Padden of Wheeler Trigg Kennedy in Denver.

By Julie A. Steinberg