On Wednesday, January 16, 2008, FDA proposed to amend its regulations governing how labeling changes may be made to an approved new drug application (NDA), biologics license application (BLA), or medical device premarket approval application (PMA). 73 Fed. Reg. 2848 (Jan. 16, 2008). FDA’s proposal has attracted significant attention, and, if adopted as proposed, could have important implications on whether FDA regulation of product labeling preempts state product liability claims.

Background and FDA’s Proposed Rule

Currently, FDA regulations provide that certain labeling changes may be communicated to FDA in a supplement to an approved application and implemented in advance of the agency’s review of the change. 21 CFR 314.70(c)(6)(iii), 21 CFR 601.12(f)(2), 21 CFR 814.39(d). These supplements are commonly referred to as “changes being effected” or “CBE” supplements.

In product liability cases based on a “failure-to-warn” cause of action, plaintiffs have argued that CBE supplements allow manufacturers to initiate labeling changes as needed, without advance approval from FDA. In this way, they argue that it is fully within the discretion of the manufacturer to add safety or risk information and, thereby, warn of all known risks associated with the product. Some courts have embraced this argument, finding that FDA-approved labeling represents the “floor” or absolute minimum. For instance, in Levine v. Wyeth, the Vermont Supreme Court held that there was “no conflict between federal labeling requirements and state failure-to-warn claims. Section 314.70(c) allows, and arguably encourages, manufacturers to strengthen warnings that, despite FDA approval, are insufficient to protect consumers.”1

In amicus briefs, however, FDA has argued that this is a misinterpretation of its CBE supplement regulations; that FDA controls the content of FDA-approved labeling; and that FDA-approved labeling should preempt conflicting state law claims that the labeling is inadequate. Despite these briefs, some courts have interpreted FDA’s CBE supplement regulations so as to avoid preempting state failure-to-warn cases. In its January 2006 final rule on prescription drug labeling, FDA elevated its case-specific statements on preemption to the level of official agency policy. 71 Fed. Reg. 3922, 3936 (Jan. 24, 2006). In the preamble to the rule, the agency emphasized that it retains full authority over the content of labeling and that it must ultimately review and approve any labeling change. In addition, the agency clarified that, while a manufacturer may strengthen a labeling warning, “in practice manufacturers typically consult with FDA to avoid implementing labeling changes with which the agency ultimately might disagree.” Id. at 3934. FDA noted that the agency’s regulations provide not merely a “floor,” but also a “ceiling” on what a manufacturer may include in its labeling. According to the agency’s interpretation of its own regulations, manufacturers have little if any opportunity to unilaterally add risk information to the labeling. Id. at 3934-35. Finally, while FDA recognized that its regulation of drug labeling “will not preempt all state law actions,” it stated that preempted claims should include any “claims that a drug’s sponsor breached an obligation to plaintiff by making a statement that FDA approved for inclusion in the drug’s label (unless FDA has made a finding that the sponsor withheld material information relating to the statement).” Id. at 3937.

However, amicus briefs and preamble statements do not impose a binding standard on the courts, and some courts have continued to disagree with FDA’s interpretation. In fact, the defendants in Levine v. Wyeth pointed to the January 2006 preamble language to support preemption, but the Vermont Supreme Court rejected Wyeth’s preemption argument reasoning that “federal labeling requirements pursuant to the FDCA create a floor, not a ceiling, for state regulation. . . . [FDA’s preamble] statement does not alter our conclusion that there is no conflict between federal objectives and Vermont common law.”2

With its proposed rule, FDA is poised to give the force and effect of law to its interpretation of 21 CFR 314.70 and other related CBE type regulations. FDA is attempting to codify “the agency’s longstanding view” that a CBE supplement is appropriate only in very limited situations: 1) “to amend the labeling for an approved product only to reflect newly acquired information” and 2) “to add or strengthen a contraindication, warning, precaution, or adverse reaction only if there is sufficient evidence of a causal association with the drug, biologic, or medical device.” 73 Fed. Reg. 2848, 2849 (Jan. 16, 2008).

FDA understands “newly acquired” information to consist of data, analyses (including metaanalyses), or other information not previously submitted to the agency that provides novel information about the product. Id. at 2850. For instance, a postmarket study that demonstrates that an approved product has a more severe risk of an adverse reaction, or reports of unique adverse events or events that are different in type, severity, or frequency may be “newly acquired” information and a CBE supplement may be appropriate to implement a labeling change. Id.

Comments on the proposed amendments must be submitted to FDA by March 17, 2008. Industry can expect the plaintiff’s bar to be very active in this rulemaking. For instance, on the same day FDA proposed the amendments, the American Association for Justice (formerly the known as the Association of Trial Lawyers of America) issued a press release demanding FDA withdraw the proposed rule.3 One week later, on January 23, eight democratic lawmakers wrote FDA Commissioner Andrew von Eschenbach expressing concern that the “intent of [FDA’s] proposal is to protect companies . . . from being held liable for marketing products they know are unsafe” and urging FDA to revoke its proposed rule.4 Among other things, the letter asked FDA to justify devoting the agency’s scarce resources to amending the current regulations governing CBE supplements and argued that the proposed rule is a departure from agency policy and counter to Congressional intent.

Implications for Preemption

As discussed above, if finalized, this rule would give FDA’s interpretation of the regulations governing CBE supplements the force and effect of law, which would strengthen the preemption defense in failure-to-warn cases that rely on the existing regulatory language.

It is also important to recognize how the proposed rule would be impacted by the reporting requirements under the Food and Drug Administration Amendments Act of 2007 (FDAAA). With the data reporting requirements under FDAAA, there should be few if any instances in which “newly acquired” safety data will be available solely to a sponsor. In other words, under the proposed rule, a sponsor should be in a position to assert that there is no relevant “newly acquired” safety data and, thus, that it could not use the CBE mechanism to unilaterally add to or strengthen its safety-related labeling. In turn, any state failure-to-warn claim, based on the argument that the sponsor had the discretion to strengthen its labeling, would be in direct conflict with federal labeling requirements.

Also, FDA’s proposed rule should be read alongside the “Rule of Construction” under FDAAA, which provides that the agency’s authority to require amendments to the labeling of an approved drug “shall not be construed to affect the responsibility of the responsible person . . . to maintain its label in accordance with existing requirements, including . . . [21 CFR] 314.70 and 601.12 . . . .” Now, the agency has proposed to revise, or at least clarify, “existing” labeling requirements. While the agency is likely acting within its legal and administrative discretion, the speed with which the agency acted to revise its labeling requirements – so soon after the passage of FDAAA – has not been lost on key lawmakers. The eight Democratic lawmakers, who have urged FDA to revoke the proposed rule, have also asserted that the purpose of the “Rule of Construction” in FDAAA was “to preserve the fundamental premises of the CBE regulations” and “to preserve the responsibility of drug companies to promptly update their own product labels to reflect the most current safety information available.” See supra note 4

Finally, FDA’s proposed rule may play a role in the U.S. Supreme Court’s consideration of the preemption issue. On Friday, January 18, 2008 – three days after the publication date of the proposed rule – the Court granted certiorari to Wyeth v. Levine to review the Vermont Supreme Court decision discussed above. Wyeth v. Levine joins Riegel v. Medtronic, in which the court examines the question of whether FDA pre-market approval of a device protects the manufacturer from certain state product liability claims, and Warner-Lambert v. Kent, where the court examines whether federal law preempts a Michigan statute that permits plaintiffs to pursue product liability suits against a manufacturer if the manufacturer defrauded FDA. The Court’s decisions in these cases will likely impact the course of FDA’s proposal.