US top court says FDA preempts state liability laws for defective generic drugs
This article was originally published in SRA
The US Supreme Court on 24 June clamped down on lawsuits filed by patients claiming injuries from design defects in generic drugs, with the 5-4 majority of the court declaring that Food and Drug Administration approval preempts a state's liability laws – handing a major legal win to the pharmaceutical industry1.
The court ruling reverses a decision by the US Court of Appeals for the First Circuit, which affirmed a $21 million jury award to a New Hampshire woman, who claimed the adverse reaction she experienced after taking Mutual Pharmaceutical's sulindac, a generic form of Merck's nonsteroidal anti-inflammatory drug (NSAID) Clinoril, was due to the medicine's flawed design2. The adverse reaction cited in Mutual Pharmaceutical Co Inc v Bartlett, was blindness and scarring related to the acute case of toxic epidermal necrolysis (TEN), a severe form of Steven's-Johnson syndrome (SJS).
Before the Supreme Court's ruling, two former FDA commissioners had contended that a win for Mutual would essentially relieve biopharmaceutical manufacturers of their responsibility for safety – putting that burden squarely on the shoulders of drug regulators3.
Drs Donald Kennedy, FDA chief from 1977-79, and David Kessler, commissioner from 1990-97, insisted in a brief filed with the court that state tort litigation "plays an indispensable role in achieving the congressional goal" of the Food, Drug & Cosmetic Act (FDCA) to "protect consumers from dangerous products."
However, Ralph Neas, president and CEO of the Generic Pharmaceutical Association, argued that the Supreme Court's 24 June ruling "upholds a key principle" that decisions about the safety and efficacy of prescription drugs "should rest with scientific experts" at the FDA, which he said is "best equipped to make judgments" affecting medicines prescribed as often as sulindac – more than 300 million times between 2007-2012.
The FDA's "expert determination," the Pharmaceutical Research and Manufacturers of America told Scrip Regulatory Affairs sister publication Scrip Intelligence, "should not be upended by a non-exert jury’s own benefit-risk assessment."
In writing for the majority, Justice Samuel Alito said state law design-defect claims that turn on the adequacy of a drug's warnings are preempted by federal law under the Supreme Court's June 2011 ruling in a consolidated case known as Pliva v Mensing and Actavis v Demahy. In this case, the high court, also in a 5-4 decision, said generic drug makers do not have the same obligations as brand-name manufacturers to update product labeling when new risks come to light4.
In a 24 June media briefing with reporters, Allison Zieve of the consumer advocacy group Public Citizen pointed out that 80% of prescriptions in the US are filled with generics. Yet, 434 of those medicines have no brand-name product remaining on the market – meaning it is unlikely new safety information will be updated in the generic labeling.
The latest matter before the Supreme Court, which heard oral arguments in March, involved New Hampshire resident Karen Bartlett, who was prescribed sulindac in 2004. At that time, the drug's labeling did not specifically refer to SJS or TEN, but did warn the prescription medicine could cause "severe skin reactions" and fatalities. However, SJS and TEN were listed as potential adverse reactions on the drug’s package insert.
The FDA in 2005 called for drug makers to update the labeling for all NSAIDS to alert prescribers and patients about the risk of TEN.
When Ms Bartlett initially sued, she asserted both failure-to-warn and design-defect claims. But the district court dismissed her failure-to-warn claim based on her doctor's admission he had not read the box label or insert for sulindac.
After a 2-week trial of the design-defect claim, a jury found Mutual liable and awarded Ms Bartlett over $21 million in damages.
In affirming the jury's award, the First Circuit said neither the FDCA nor the FDA's regulations preempted Ms Bartlett's design-defect claims and that the Supreme Court's decision in Pliva did not apply to the sulindac case because the New Hampshire woman's arguments were based on the product's design and not the warnings in the medicine's labeling.
While the generic maker had no choice as to labeling, the decision to make the drug and market it in New Hampshire was "wholly its own," the First Circuit said, insisting Mutual and other generics manufacturers facing design-defect claims could comply with both federal and state laws simply by choosing not to make the drug at all.
Unlike in Pliva, compliance with both federal and state law is not impossible in the Mutual case because New Hampshire law does not require the generic maker to take any action that federal law prohibits, the appeals court concluded.
New Hampshire's law "imposes liability for selling any product in a defective condition unreasonably dangerous to the user or consumer when the product causes injury to the user or consumer," the First Circuit court said.
However, Justice Alito declared that under the Supremacy Clause of the US Constitution, state laws that conflict with federal law are "without effect."
The FDCA requires a generic drug to have the same active ingredients, route of administration, dosage form, strength and labeling as its brand-name drug equivalent and because of sulindac's simple composition, the drug is "chemically incapable of being redesigned," Justice Alito insisted.
Accordingly, because redesign was "impossible," Mutual could only ameliorate sulindac's "risk-utility" profile by strengthening its warnings, he said. Thus, New Hampshire's law ultimately would have required Mutual to change sulindac's labeling.
"But Pliva makes clear" that federal law prevents generic drug manufacturers from changing their labels, and accordingly, Mutual was prohibited from taking the remedial action required to avoid liability under New Hampshire law, Justice Alito pointed out."Because it was impossible for Mutual to comply with both state and federal law, New Hampshire's warning-based design-defect cause of action is preempted with respect to FDA-approved drugs sold in interstate commerce," he said.
In reversing the lower court's ruling, Justice Alito, who was joined in the majority by Chief Justice John Roberts and Justices Antonin Scalia, Anthony Kennedy and Clarence Thomas, said the First Circuit's rationale that Mutual could escape the impossibility of complying with both its federal and state law duties by choosing to stop selling sulindac was "incompatible" with the Supreme Court' preemption cases, "which have presumed that an actor seeking to satisfy both federal and state law obligations is not required to cease acting altogether."
Nonetheless, Justice Alito acknowledged the case arose out of "tragic circumstances" blaming it on a "combination of factors," including the FDA's decision to approve the sale of sulindac and the warnings that accompanied it at the time it was prescribed; the decision by Ms Bartlett's physician to prescribe the drug, despite its known risks; and Congress' decision to regulate the manufacture and sale of generic drugs in a way that reduces their cost to patients but leaves generic manufacturers "incapable of modifying either the drugs' compositions or their warnings."
While Ms Bartlett's case "evokes deep sympathy," Justice Alito said a "straightforward application of preemption law requires" the Supreme Court to reverse the First Circuit's decision.
The Mutual case drew two separate dissenting opinions – one authored by Justice Stephen Breyer, joined by Justice Elena Kagan, and the other by Justice Sonia Sotomayor, joined by Justice Ruth Bader Ginsburg.
Justice Breyer asserted is it "not literally impossible" for Mutual and other generic drug makers to comply with conflicting state and federal law. "I have found no convincing reason to believe that removing this particular drug from New Hampshire’s market, or requiring damage payments for it there, would be so harmful that it would seriously undercut the purposes of the federal statutory scheme," he argued.
Justice Breyer also scolded the FDA for not holding any hearings on the matter of conflicts between state and federal laws or soliciting the opinions, arguments and views of the public in other ways.
He added that the FDA has set forth conflicting positions on preemption – finding no preemption in Wyeth v Levine, in which the Supreme Court said US approval of the drug company's nausea and motion sickness medicine Phenergan (promethazine) did not preempt the right of a Vermont musician Diana Levine to sue a manufacturer in state court if the product causes injury5, yet taking the opposite view in Mutual and Pliva.
In ruling in Mutual's favor, Justice Sotomayor asserted the Supreme Court "unnecessarily and unwisely extends its holding" in Pliva to preempt New Hampshire's law. "This expanded notion of impossibility preemption threatens to disturb a considerable amount of state law," Justice Sotomayor argued.
"State design-defect laws play an important role not only in discovering risks, but also in providing incentives for manufacturers to remove dangerous products from the market promptly," she contended. "If manufacturers of products that require preapproval are given de facto immunity from design-defect liability, then the public will have to rely exclusively on imperfect federal agencies with limited resources and sometimes limited legal authority to recall approved products. And consumers injured by those products will have no recourse."
While the Court "laments" Ms Bartlett's "tragic" situation, the responsibility for the fact she has been "deprived of a remedy for her injuries rests with this court,” Justice Sotomayor argued.
"If our established preemption principles were properly applied in this case, and if New Hampshire law were correctly construed, then federal law would pose no barrier to Karen Bartlett's recovery,” she concluded.
In light of the Mutual decision, a bicameral group of House of Representatives and Senate lawmakers, led by Henry Waxman (Democrat-California) – co-author of the Hatch-Waxman Act – called on FDA Commissioner Dr Margaret Hamburg to revise the agency’s regulations to enable generic makers to update drug labeling to ensure the public is informed of risks and benefits of the medicines.
The outcome in Mutual, the lawmakers said, “penalizes the millions of Americans across the country who rely on the generic versions of prescription drugs and jeopardizes our nation’s commitment to promoting safe, affordable generic medications.”
References
1. US Supreme Court, Mutual Pharmaceutical Co Inc v Bartlett, 24 June 2013, www.supremecourt.gov/opinions/12pdf/12-142_8njq.pdf
2. SCOTUS hears "spirited" arguments in generic "flawed design" case, Scrip Regulatory Affairs, 21 March 2013
3. Turning Hatch-Waxman on its head for generic drug makers? US court cases imminent, Scrip Regulatory Affairs, 11 March 2013
4. US legislation seeks to give generics labelling change abilities, Scrip Regulatory Affairs, 24 April 2012
5. Haston T, Navigating Regulatory Waters in the Wake of Wyeth v Levine, Scrip Regulatory Affairs, 1 September 2009