Medical Device Daily Washington Editor
WASHINGTON — The issue of FDA pre-emption of state regulatory authority – and by extension of state liability law – has stuck out like a sore thumb of late, but the issue has two dimensions. One is that of expressed pre-emption via the Medical Device Amendments of 1976, which now applies only to PMA devices, and the other is implied pre-emption as was addressed in the recent case of Wyeth v. Levine.
However, if Congress passes the Medical Device Safety Act, PMA pre-emption will vanish and the question of PMA device labels will be reborn. At least one speaker at last week's FDA Regulatory and Compliance symposium believes that the agency may default to prescription drug labeling standards to address labels for PMA devices in that scenario. In that event, a logical tension between various labeling requirements that currently is a non-issue for PMA devices may suddenly become a very relevant and nettlesome issue.
Sheldon Bradshaw of the law firm of Hunton & Williams (Washington) told attendees at the FDA Symposium that the Supreme Court's decision in Levine is decidedly at odds with FDA's approach to risk information in product labels.
Bradshaw reminded attendees that PMA pre-emption "might not be with us much longer, and that makes the Levine case" much more important inasmuch as device liability law would presumably default to the concepts underlying the Levine case. He also reminded the audience that pre-emption as understood in the Medical Device Amendments of 1976 was overturned for 510(k) devices in the 1990s.
Bradshaw observed that "FDA set forth its position on pre-emption" for drugs and biologics via the preamble to the physician labeling rule published in 2006. Despite the agency's explicit position, "the Supreme Court gave no deference" to FDA in the Levine decision, Bradshaw noted. He said, "the purpose [of the rule] was to dramatically change and alter the format and layout" of labels, an action he said FDA undertook "after years of research to figure out how doctors perceive labeling ... and what problems doctors were having with the existing format."
According to Bradshaw, some stakeholders told FDA at the time, "if we add this new highlight section to the front of the label, we're going to subject ourselves to lawsuits" because doctors might not read the balance of the label after reviewing the highlights section, which was largely the emphasis of the January 2006 rule. "The agency tried to explain why it did not believe" the concerns were credible, "then set forth six different categories FDA believed would be pre-empted" under the labeling rule, he said.
Bradshaw said that the first category of FDA's promised safe harbor meant that "you're not going to be subject to a product liability claim" in a failure-to-warn lawsuit if the litigant bases his or her case on a failure to include in the highlight section any warnings or contraindications that appear elsewhere in the label.
Another key pre-emptive element in the guidance was the one that indemnified firms from lawsuits based on a failure to include contraindications and warnings not supported by evidence. Bradshaw noted that FDA's view is that contraindications and warnings "must address 'known hazards and not theoretical possibilities."
Bradshaw also made note of an inherent conflict that would be encountered in any effort to unilaterally add a warning to the body of the label via a changes-being-effected (CBE) supplement, perhaps the most vexing feature of the situation. Given that industry is not permitted to make unilateral changes to the highlights section of a label, and given that all contraindications and warnings in the body of the label must appear in the highlights section, manufacturers are in a Catch-22. Hence, firms are "not allowed to make any changes to the highlight section through the CBE," Bradshaw said. This inability to change the label unilaterally served as a defense offered by Wyeth (Madison, New Jersey) in the Levine case, a strategy that obviously failed the firm.
The labeling changes incurred by the 2006 FDA memo explicitly address 21 CFR Part 211, which deals with pharmaceutical labels rather than Part 801, which deals with device labels, but one of the speakers at the FDA Symposium, Howard Dorfman of the New York law firm of Ropes & Gray, told Medical Device Daily that several circumstances are nonetheless likely to drive device label standards toward those for drug labels. "I think that as far as labeling is concerned, particularly because of the increasing pressure on the agency to tighten up all activity related to safety (including labeling and communication of safety-related information), you're going to start seeing a narrowing of the distinctions between the two, particularly with respect to labeling," he said.
"Obviously the initial focus has been on pharmaceuticals," Dorfman observed, but "as increased safety concerns manifest themselves ... I think you're going to see FDA activity related to medical devices" start to resemble those for drugs.
By some accounts, FDA's motive for the drug labeling guidance was that the agency was increasingly called on to file briefs for a number of liability cases and wanted to clarify the relationship between FDA's regulatory powers and state law. Dorfman confirmed that this belief is widely held.
"At that time, you had a number of those at FDA who were aggressive advocates for FDA as the final arbiter of safety issues," especially where labeling is concerned, Dorfman noted. Given that the product liability system "left unchecked would result in the potential for lay juries in 50 jurisdictions ... to basically assert what a final label should or should not be," FDA "became much more aggressive about filing amicus briefs" that clarified "the role of FDA and the detailed analysis and review" undertaken by agency reviewers on such matters. This culminated in the preamble, "which the Supreme Court in the Levine case pays scant attention to."
One view of Levine might hold that it's simply another round in the ongoing wrestling match between the states and the federal government over federal pre-emption, but Dorfman said the Supreme Court did not necessarily look at the case solely in that context. The decision, he said, was "partly a reaction to a concern that unless there was express statutory language for pre-emption," a finding for pre-emption "would potentially have long-term consequences for tort liability" and the ability of injured plaintiffs "to assert their rights in court, as some commentators had suggested."
As to whether the new FDA leadership might see the 2006 guidance as unnecessary and hence be inclined to withdraw it, Dorfman said, "I don't think they feel they have to," but any interest on the agency's part would likely be overborne by a raft of other issues on the agency's agenda. Furthermore, "because the Supreme Court was so clear in its decision, there is less need ... to take action" with regard to this document.
Makers of high-risk devices might be inclined to wonder how all these questions about labeling might work into off-label use of those devices. Dorfman observed, "There have been suggestions that companies provide within their labeling the relevant safety information that could be inferred as reflecting potential off-label use."
FDA has taken the position that labeling should reflect the known potential adverse effects of a given therapy and has approved such labeling where the agency believes it is appropriate. Nevertheless, FDA approval of such information in the label would require that it be worded "in a way that is totally non-promotional," and could not serve as a basis for any promotional activity of such uses, Dorfman commented.
"The main thing to remember is that there's a huge distinction between providing medically relevant and authoritative information ... and a concerted promotional campaign that fosters off-label use," Dorfman remarked, adding, "if there are safety concerns the company is aware of" via medical device reports and other sources, the company "will be able to provide useful safety information to a physician" in various communication mechanisms, including potentially in an FDA-approved label, so long as there is no company generated language that "would in any way suggest or condone off-label use."
Mark McCarty, 703-268-5690;