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Clearing Up ‘Clear Evidence’ and Implications for Labeling Post-Merck Decision


Pharmaceutical Executive

Intellectual property attorneys discuss the clarified requirements for when state failure-to-warn claims are pre-empted by FDA regulations after the Supreme Court Merck case.

In the recently decided Merck Sharp & Dohme Corporation v. Albrecht et al., the Supreme Court clarified the requirements for when state failure-to-warn claims are pre-empted by FDA regulations. Merck, the manufacturer of Fosamax, a drug that treats and prevents osteoporosis in postmenopausal women, was sued under a state failure-to-warn law for not including in its labeling that atypical femoral fractures were a risk of taking Fosamax. While the label was amended in 2011 to include this warning, more than 500 individuals that took Fosamax between 1999 and 2010 suffered atypical femoral fractures. In its defense, Merck argued that the state-law failure-to-warn claim was pre-empted by federal law.

Conceding that the FDA regulations would have allowed Merck to try to change its label to include the warning prior to 2010, Merck asserted that the FDA would have rejected the attempt to change the Fosamax label. Merck argued that the FDA would have rejected an attempt to include a warning for atypical femoral fractures in its Fosamax label, because in 2008 the FDA rejected an attempt by Merck to amend the Fosamax label to include a warning for the risk of stress fractures. The District Court agreed with Merck, but the Third Circuit vacated and remanded.

The Court’s holding in Merck is an elaboration of the holding in Wyeth v. Levine, which held that a state-law failure-to-warn claim is pre-empted where there is “clear evidence” that the FDA would not have approved a change to the label. The Merck opinion does not change the current state of the law set forth in Wyeth, but rather provides what is necessary to show clear evidence that the FDA would not have approved a change to a drug’s label.

Justice Breyer delivered the opinion of the Court, which held that “clear evidence” is evidence that shows that the drug manufacturer fully informed the FDA of the justifications for the warning required by state law and that the FDA informed the drug manufacturer that the FDA would not approve a change to the drug’s label to include the warning. Additionally, the Court held that the pre-emption issue, which in this case is a question of agency disapproval, is primarily a question of law that should be decided by a judge, not a jury.

Therefore, to meet the “clear evidence” standard set forth in Wyeth, a drug manufacture arguing that an FDA decision pre-empts a state failure-to-warn law must now show that it fully informed the FDA as to why the label needed to be changed to conform with state law; and also that the FDA, in turn, informed the drug manufacturer that it would not approve changing the label to include the warning.

Under this decision, reference product drug manufacturers must now be diligent in proposing label amendments when there is data available demonstrating a connection between serious adverse events and the drug in question. Reference product drug manufacturers must now become intimately familiar with the mechanisms used to amend a label, whether through an immediate Changes Being Effected amendment or a Prior Approval Supplement, as the type of mechanism is important and is dependent on the nature of the change to the label. In addition to the mechanisms of amendment, drug manufactures must also pay closer attention to safety data generated post approval.

As far as generic drug manufacturers are concerned, they are still required to provide labels that are “the same” as the label for the reference listed drug. Generic manufacturers should thus keep their eyes open for amendments to reference product labels. More frequent amendments to reference product labels are likely going to be filed in light of Merck.


Kevin Nelson, partner, Schiff Hardin
Chad Watson, associate, Schiff Hardin



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