An upcoming U.S. Supreme Court decision and a new report by Congress will be setting the stage for congressional attention to federal drug-labeling rules. Having given the Food and Drug Administration (FDA) new authority in 2006 to force drug-labeling changes quickly as part of the FDA Amendments Act (FDAAA), it is becoming clear that the House and Senate will have to review the matter again, this time with a sharper, Democratic-edged shovel. Ideas that were excluded from the FDAAA because of opposition by Republicans and the Bush administration are likely to be revisited and approved. These actions include allowing consumers to sue pharmaceutical companies in state courts over drug labels.
A major concern in the Supreme Court case is whether Wyeth Pharmaceuticals should have changed the label on its anti-nausea drug Phenergan (promethazine) without the FDA’s approval. The FDA currently has a “changes being effected” (CBE) labeling regulation—21 C.F.R. §314.70(c)—that specifies when drug manufacturers can make quick changes to labels, such as strengthening safety language, without the agency’s prior approval. That CBE rule was the subject of a scathing report from Representative Henry Waxman (D-Calif.) in late October and was a side issue in a Supreme Court hearing in early November.
Drug companies are often eager to make CBE changes to avoid lawsuits that might charge them with negligence. However, the Bush FDA has narrowed the grounds for CBE changes because it wants to keep drug companies from making “overly cautious” statements about risk in order to avoid lawsuits. Those guarded statements might dissuade physicians and consumers from using a drug that has actual benefits for many people and whose risks have been acknowledged by the FDA, which has concluded that the benefits outweigh the risks.
At one level, the Supreme Court case demonstrates the need for pharmacists to read drug labels more carefully. A Vermont resident, Diana Levine, sued physicians and staff members at a local hospital for malpractice. She claimed that they had carelessly administered Wyeth’s anti-nausea drug promethazine (Phenergan) contrary to label instructions pertaining to the intravenous (IV-push) method of administration. Her arm below the elbow had to be amputated because of gangrene that resulted from the drug’s entering an artery.
The hospital and its staff settled the malpractice suit out of court. Ms. Levine then sued Wyeth in state court, arguing the company should have, on its own, made CBE label changes by withdrawing the IV-push method. Wyeth claimed that the risks of IV-push medications are clearly spelled out on the label and that the method has more benefits than risks. IV-push medications must be correctly diluted and given at the right speed along with appropriate monitoring.
Ms. Levine also claimed that although the Wyeth label had been fully approved by the FDA, she should still be able to collect from Wyeth under a Vermont law that is more lenient toward plaintiffs than the federal law (the Food, Drug and Cosmetics Act). The Vermont court awarded Ms. Levine $7.4 million. Wyeth appealed to the U.S. Supreme Court, claiming that the federal drug-labeling law pre-empted state law.
The Supreme Court probably won’t make a decision until the end of its term, in summer 2009. The court will determine whether drug companies can be sued in state court over labeling approved by the FDA. The court might not address the CBE issue, however, which is part of the case and at the heart of the Waxman report, which also touches on the pre-emption matter.
The report issued by Representative Waxman’s House Oversight and Investigations Committee in late October argued that the FDA had recently restricted CBE authority twice—one time as part of the 2006 Physician Labeling Rule and a second time in a CBE rule issued in August 2008. The Waxman report was controversial because it said that top FDA officials in career safety had warned against circumscribing CBE authority, but Bush administration political appointees in the Office of the General Counsel went ahead anyway.
Complicating the FDA’s tightening of the CBE rule in 2006 and 2008 was another factor: at the same time, in both rulings, the FDA also included pre-emption language stating that consumers could not sue a drug company for “failure to warn” in state court based on a state law. The Waxman report quoted John Jenkins, MD, Director of the Office of New Drugs (OND), in the Center for Drug Evaluation and Research (CDER), who sent comments to Jane Axelrad, JD, Associate Director for Policy in CDER. On May 22, 2003, as the pre-emption policy was being developed, Dr. Jenkins wrote:
The premise of the basis for much of the argument for why we are proposing to invoke preemption seems to be based on a false assumption that the FDA approved labeling is fully accurate and up-to-date in a real time basis. We know that such an assumption is false.
Both the Supreme Court case and the Waxman report underscore the necessity for pharmacists to scrutinize label instructions, even with drugs like promethazine, which has been around since the 1950s. Pharmacists should also be aware of any controversies relating to the adverse effects of particular drugs or to information that might not be reflected in the labeling, such as the IV-push method used with promethazine.