FDA Proposes to Codify Longstanding Policy for Making Labeling Changes for Approved Drugs, Biologics, and Medical Devices; Change Could Significantly Affect Preemption Defenses

On January 16, 2008, FDA issued a proposed rule that would “reaffirm [the Agency’s] longstanding position that” labeling changes for approved drugs, biologics, and medical devices may only be made to show newly acquired information or to “add or strengthen a contraindication, warning, precaution, or adverse reaction” when there is sufficient evidence to support the change.

FDA’s current regulations at 21 C.F.R. §§ 314.70(c), 601.12(f), and 814.39(d) allow changes to be made to drug, biologic, and device labeling in certain situations upon FDA’s receipt of a supplemental application, commonly referred to as a “changes being effect supplement,” or a “CBE supplement,” for drugs and biologics, and a Premarket Approval Application (“PMA”) supplement or Special PMA Supplement for devices.(For convenience, we use the term CBE supplement to refer to drug, biologic, and device labeling supplements.) FDA’s proposal, if finalized, would make explicit that CBEs may only be used to update newly acquired safety information, which FDA proposed to define as “data, analyses, or other information not previously submitted to the agency, or submitted within a reasonable time period prior to the CBE supplement, that provides novel information about the product.”For example, if a postmarket study suggests a more severe and significant adverse reaction than previously known, then a CBE supplement “may be appropriate;” but if a study only provides additional data on a known adverse reaction, a CBE supplement would not be appropriate.Further, according to FDA, a CBE supplement may only be used for labeling changes relating to “contraindications, warnings, precautions, or adverse reactions in circumstances when there is sufficient evidence of a causal association with the drug, biologic, or medical device.”

Because FDA’s proposal would merely codify existing FDA policy, it would not significantly alter Agency practice or establish new regulatory requirements.However, the proposed rule, if finalized, could give significant support to firms that invoke an FDA preemption defense in product liability cases where plaintiffs argue that firms should revise their own labeling in accordance with state law.Specifically, by revising its CBE supplement regulations to state that such applications require “newly acquired information,” FDA could limit the number of cases in which the results from certain studies could be used to support a stronger labeling warning and a product liability lawsuit.FDA states in the proposal that:

To the extent that state law would require a sponsor to add information to the labeling for an approved drug or biologic without advance FDA approval based on information or data as to risks that are similar in type or severity to those previously submitted to the FDA, or based on information or data that does not provide sufficient evidence of a causal association with the product, such a state requirement would conflict with federal law. In such a situation, it would be impossible to market a product in compliance with both federal and state law, and the state law would “stand[] as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress,” Hines, 312 U.S. at 67.Moreover, such a state law requirement relating to a medical device would constitute a requirement that is different from, or in addition to, a federal requirement applicable to the device, and which relates to the safety or effectiveness of the device. 21 U.S.C. 360k(a).

Indeed, this is precisely the issue the Supreme Court will consider later this year in Wyeth v. Levine - whether prescription drug labeling preempts state law product liability claims.Documents on the case are available from SCOTUSBlog.Last week, the Court agreed to hear the case.

In 2006, the Vermont Supreme Court ruled against Wyeth concerning the company’s labeling of PHENERGAN (promethazine HCl) and held that the FDC Act “provides a floor, not a ceiling, for state regulation.”FDA has previously stated (pages 3934-35) that “FDA approval of labeling under the [FDC Act] . . . preempts conflicting or contrary State law,” and that “FDA interprets the [FDC Act] to establish both a ‘floor’ and a ‘ceiling,’ such that additional disclosures of risk information can expose a manufacturer to liability under the act if the additional statement is unsubstantiated or otherwise false or misleading.”

FDA has invited comments on the Agency’s proposal regarding when safety information relating to a drug, biologic, or medical device should be considered “newly acquired.”All comments to the proposed rule are due March 17.