WASHINGTON -- The U.S. Supreme Court will hear arguments on Wednesday in a case involving generic drugmakers' responsibility to provide safety information in product labeling.
The case -- Pliva, Inc. v. Mensing (which has been consolidated with Actavis Elizabeth LLC v. Mensing, and Actavis, Inc. v. Demahy) -- centers around Gladys Mensing, a Minnesota woman who was prescribed metoclopramide (Reglan) in 2001 to treat her diabetic gastroparesis. Her pharmacist filled her prescription with a generic version of the drug.
After taking the generic for four years, Mensing developed tardive dyskinesia and sued Pliva and Actavis, the makers of the generic, arguing that although there was growing evidence that long-term metoclopramide use carried a risk for tardive dyskinesia that was far greater than indicated on the drugs' label, no metoclopramide manufacturer took steps to change label warnings.
Mensing had also sued Wyeth Pharmaceuticals, maker of the brand-name drug for fraud, alleging that Wyeth's label didn't accurately reflect the tardive dyskinesia risk, and her physicians consulted that label when writing Mensing's prescription. But a Minnesota appeals court dismissed the suit against Wyeth, because Mensing never took any brand-name metoclopramide.
The Hatch-Waxman amendments to the Food, Drug, and Cosmetic Act provided an abbreviated pathway for generic drugs that doesn't require generic manufacturers to repeat the same costly trials conducted by brand-name manufacturers. But generic drugs must carry identical labels as their branded versions. If a brand-name drugmaker updates its label as new risks become apparent, the generic drugmaker must do the same.
Mensing is arguing the generic makers of metoclopramide knew of the increased risk for tardive dyskinesia.
"The regulatory framework makes clear that a generic manufacturer must take steps to warn its customers when it learns it may be marketing an unsafe drug," Minnesota appeals court judges argued in an earlier decision.
Identical Labeling Required
Under law, generic manufacturers are subject to the requirement that their labeling "shall be revised as soon as there is reasonable evidence of an association of a serious hazard with a drug." The FDA would have to sign off on the updated labeling.
But the makers of the generic drug argue that they could not have delivered whatever additional warnings state law required while remaining faithful to the Hatch-Waxman amendment, which require a drug's approved labeling be identical to the brand-name drug's approved labeling.
"This is somewhat of a sticky wicket," Bob Billings, interim executive director of the Generic Pharmaceutical Association (GPhA), told MedPage Today. " We are required to label our products the same as the brand is labeled.
"When FDA approves [a generic] we're basing [the generic] on the brand-name clinical trials. Generics don't have to do the clinical trials; that's why they're less costly. In terms of all the proprietary data, we're not privy to that data. We have to rely on what they show on their label."
Billings added that GPhA, which filed a friend-of-the-court brief on behalf of the two generic drug companies involved in the suit -- Pliva, a Croatian company now owned by Barr Laboratories, and Actavis, a Swiss company -- "absolutely 100% believes that patient safety is paramount."
Feds Say FDA Needed Notice
But lawyers for the departments of Justice and Health and Human Services don't buy GPhA's reasoning. The generic manufacturers should have provided the FDA with the relevant safety information and allowed the FDA to determine whether the labeling should be revised, they wrote in a amicus brief filed on behalf of Mensing and Julie Demahy, the other patient in the lawsuit who had a very similar experience to Mensing's.
Generic drugmakers "have a duty under federal law to propose appropriate changes to approved labeling to communicate warnings about serious drug hazards," the administration lawyers wrote.
The case recalls the 2009
Wyeth v. Levine case, in which the Supreme Court sided with Diana Levine, a musician who lost her arm when gangrene developed following injection of the anti-nausea drug promethazine (Phenergan) by IV push. The Court ruled against Wyeth, the maker of Phenergan, in its ruling that FDA approval of a drug and its label does not shield its maker from lawsuits brought by patients injured by use of the drug.
The generic defendants in the current case would argue that the Wyeth case is different because it dealt with brand-name drugs.
But as the Minnesota appeals court judges pointed out in their decision, the Wyeth case highlights the "central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times. It is charged both with crafting an adequate label and with ensuring that its warnings remain adequate."
Physician Groups Side With Mensing
In addition to the Obama administration, 42 states and the District of Columbia; the American Medical Association (AMA), along with a number of state medical associations; and the American Association of Justice (AAJ) have all filed amicus briefs on behalf of the injured women in Pliva v. Mensing.
"Interestingly, this case is pretty much the generic drug companies against the world," said Louis Bograd, a lawyer with the Center for Constitutional Litigation, who is arguing before the Supreme Court on behalf of Mensing and Demahy. AAJ held a Thursday afternoon teleconference to discuss the case.
In its brief, the AMA said physicians must rely on knowledge of current and accurate drug safety information in order to safely and effectively prescribe prescription drugs.
"It would disrupt the established patient care system to adopt a policy pursuant to which one member of the healthcare community -- generic drug manufacturers -- was permitted to absolve themselves of their unique and vital role in ongoing drug safety," AMA lawyers wrote.
Christy Graves, MD, the physician who prescribed metoclopramide to Demahy, also filed a friend-of-the-court brief. Graves, a internist in Louisiana, said she never would have continued to prescribe Demahy metoclopramide for four years for her gastroesophageal reflux disorder if she had known of the tardive dyskinesia risk. The metoclopramide label warned only of a very small risk of adverse neurological reactions.
From 1985 through 2009, the warnings on metoclopramide stated it carried a risk of 1 in 500 patients developing a class of neurological side effects called extrapyramidal symptoms, including tardive dyskinesia. But after the risk was found to be much higher, the FDA in 2009 required makers of metoclopramide add a
boxed warning to their drug labels regarding the risk of tardive dyskinesia with long-term or high-dose use.
In the GPhA amicus brief on behalf of Pliva and Actavis, the group argues that because generics are essentially the same as the brand-name competitors, "that generic manufacturers thus should not be forced to assume the extraordinary burden of generating, compiling, and continuously revisiting the clinical data necessary to justify the FDA-approved labeling that federal law compels them to put on their products."
If the Supreme Court ultimately rules against the generic companies, it could raise the costs of producing generic drugs, which could be passed on to patients, Billings said
