Stage Set for Merck’s SCOTUS Case Over Warnings in Labels

Regulatory NewsRegulatory News | 10 December 2018 |  By 

With the acting solicitor general set to participate in oral arguments before the Supreme Court on 7 January, the high court will be deciding a contentious case centered on who has the final say in warning labels on pharmaceuticals.

The case, known as Merck v. Albrecht, presents the question of whether Merck should be held liable for failing to warn about the side effects of an osteoporosis drug, despite attempting to change the warning label and having FDA reject its proposal.


Brand-name drug manufacturers bear responsibility for the content of labels – meaning that when new information becomes available about a new risk that causes existing labeling to become out of date, the manufacturer is responsible for pursuing a revision.

Two mechanisms exist for changing a brand-name drug's labeling, both of which require that the manufacturer file a supplemental new drug application (NDA). Sponsors may submit a Changes Being Effected (CBE) supplement or a Prior Approval Supplement (PAS).

In this case, in June 2008, FDA informed Merck that it was aware of reports regarding the occurrence of fractures in patients using bisphosphonates like Fosamax (alendronate sodium). Three months later, in September 2008, Merck submitted three PAS for its three Fosamax products, supporting its applications with evidence regarding femoral fractures.

But in May 2009, FDA issued a Complete Response Letter informing Merck that FDA could not "approve the applications in their present form." One month later, Merck updated the Adverse Reactions section of its Fosamax labeling using FDA's recommended text, then withdrew its three pending PASs and submitted new CBE supplements.

Nearly a year after its Complete Response Letter, and after reviewing additional data submitted by Merck and other manufacturers, FDA issued a safety announcement in March 2010 stating that the data at that time had "not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures," but that FDA was working with a task force of outside experts to gather additional information.

In September 2010, the task force identified an association between long-term bisphosphonate use and certain atypical femoral fractures. A month later, FDA announced that it was requiring bisphosphonate manufacturers to modify their labeling to include information regarding the risk of such fractures in the Warnings and Precautions section. Shortly thereafter, FDA approved that labeling change for Fosamax.

Over 1000 people subsequently filed separate lawsuits against Merck, alleging that they had sustained femoral fractures caused by taking Fosamax, and generally alleging that Merck had failed to provide adequate warnings on its label.

A federal court sided with Merck, but in March 2017, a Pennsylvania appeals court determined that a "reasonable jury" could conclude that Merck could have revised the Warnings and Precautions section of its label before September 2010 and FDA prevented such a revision.


The Trump Administration’s lawyers argue that when FDA renders a decision declining to approve a drug labeling change, “The interpretation of that administrative decision and its significance for a failure-to-warn claim are legal questions for a court to resolve, not factual questions for a jury. Moreover, because FDA's decision here prevented petitioner from modifying the relevant labeling before late 2010, the court of appeals erred in rejecting petitioner's [Merck’s] impossibility-preemption defense.”

Industry groups PhRMA and BIO also make the claim that allowing companies to be held liable under state law for failure to include warnings expressly deemed inappropriate or unwarranted by FDA “would greatly compound that liability in a manner that both is unfair and could deter innovation.” The industry groups also called for the Supreme Court to establish “clear, consistent, and fair preemption rules for FDA-rejected warnings.”

On the other side, however, almost two dozen state attorneys general argue that Merck’s argument upsets Congress’ careful balance between federal and state regulatory authority, in an area traditionally of state concern.

“States have long regulated in the area of drug labeling. The duty to warn patients and physicians about emerging safety risks predates—by decades—the advent of federal regulation of drugs,” the attorneys argue.

In addition, they dispute that the warning Merck presented to FDA (i.e. stress fractures) encompassed the harm underlying respondents’ state tort law claims (i.e. atypical femoral fractures). In addition, Merck “has not demonstrated that the label change it proposed to the FDA would have satisfied its state law duty to warn,” the attorneys general argue.

Under Merck’s theory of preemption, the attorneys general claim, FDA’s rejection of a proposed warning based on inadequate evidence would bar later claims—even if the inadequate evidence was itself the result of the company’s own lack of diligence.

“Such an approach would reward manufacturers who fell short in their efforts to collect information about a particular risk and create incentives to learn as little as possible before proposing label changes to the FDA,” they added.


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