A U.S. Court of Appeals has held that a Food and Drug Administration (FDA) denial of a citizen petition can be “clear evidence” of conflict preemption under the test set forth by the Supreme Court in Wyeth v. Levine, 555 U.S. 555 (2009).

At issue in Cerveny v. Aventis was whether Aventis failed to warn the plaintiffs of the risk of using fertility drug Clomid to become pregnant. Victoria Cerveny took Clomid in October 1992, before her pregnancy; Alexander Cerveny was born in July 1993 with a deformity of his left elbow and only three digits on his left hand. The complaint alleged that Clomid causes birth defects in women who take it before pregnancy, in part because it has a long half-life and can remain in a woman’s blood into the second month of pregnancy.

When Clomid entered the U.S. market in 1967, its label contained a warning that “inadvertent” use of the drug during early stages of pregnancy had resulted in fetal harm in animal testing but that there was no causative evidence of risk in humans. In the mid- to late-1980s, FDA and Aventis drafted possible changes to the prescribing information accompanying Clomid that dealt primarily with the risk to women who took Clomid during pregnancy. Aventis eventually made some changes to the label, but not until after Alexander Cerveny was born. The plaintiffs claimed that had FDA’s suggested warning been on the label in 1992, Victoria Cerveny never would have taken the drug.

In 2007, a California attorney who had filed several Clomid lawsuits alleging that use of the drug before pregnancy caused birth defects submitted a citizen petition to FDA urging that the drug’s label be changed to include a warning about the teratogenic risks of the drug if it was used before pregnancy. The petition claimed that Clomid’s long half-life caused it to be “biologically active well into the second month of pregnancy” and asserted that the drug caused, among other things, congenital musculoskeletal abnormalities. FDA rejected the petition in 2009 and, after it was re-submitted, again in 2012. As Shook attorneys argued to the trial and appeals courts, FDA considered the available scientific evidence and “twice unequivocally” determined that it did not meet the regulatory standard for adding a warning. Specifically, FDA decided that the “currently available, relevant and reliable scientific evidence” did not establish that the use of Clomid before pregnancy carried teratogenic risks.

Shook attorneys moved for summary judgment on the plaintiffs’ five claims: failure to warn (strict liability); failure to warn (negligence); breach of implied warranty; negligent misrepresentation; and fraud. They argued to the Utah trial court that the claims were preempted because FDA’s rejection of the citizen petition constituted “clear evidence” that the agency would not have approved the warning that Clomid carried a risk of fetal harm if taken before pregnancy. The trial court agreed and granted Shook’s motion for all five claims.

The plaintiffs appealed, arguing that the trial court applied the Wyeth “clear evidence” test too broadly and that FDA rejection of a citizen petition, standing alone, could not be clear evidence that FDA would have rejected a manufacturer’s request to change a label under the agency’s Change Being Effected (CBE) regulation. Shook attorneys, along with amici Pharmaceutical Research and Manufacturers of America and the Biotechnology Innovation Organization, argued that FDA applies the same level of scrutiny and the same standard to changes in warning labels whether the request for change comes from a manufacturer or through a citizen petition. In addition, amici U.S. Chamber of Commerce, American Tort Reform Association and National Association of Manufacturers joined Shook’s argument that FDA regulations allow a manufacturer to change a drug label only if there is “reasonable” evidence of a causal relationship between the drug and the alleged risk.

Although the Tenth Circuit reversed and remanded some of the plaintiffs’ claims with instructions for the district court to reconsider its rulings on those, the appellate court came down squarely on the drug manufacturer’s side on the main issue. Ruling that FDA’s denial of the citizen petition was “clear evidence” on its own that the agency would not have approved a request from Aventis to add a pre-pregnancy warning label for Clomid, the Tenth Circuit upheld summary judgment on the failure-to-warn claims. The court said:

Under the same standard for manufacturer-initiated changes, the FDA rejected a citizen petition containing arguments virtually identical to the Cervenys’. We will not assume that the FDA would have scuttled its own regulatory standard if Aventis had requested the new warning.

The holding clarifies the “clear evidence” standard considered in Wyeth and provides new guidance for pharmaceutical manufacturers facing liability claims—but it does not benefit only those who can point to a relevant citizen petition. The holding rejects arguments that plaintiffs have successfully advanced in other districts courts: namely, (i) that citizens’ petitions alone can never be preemptive; and (ii) that only FDA’s denial of a manufacturer’s proposed label change can meet the “clear evidence” standard of Wyeth. This opinion should help other manufacturers faced with state-law claims that should be preempted under the Supreme Court’s opinion in Wyeth.

Cerveny v. Aventis, No. 16-4050 (10th Cir., May 2, 2017).

The decision was hailed as one of the Ten Best Prescription Drug/Medical Device Decisions of 2017 by the Drug and Device Law Blog.

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