Amendments Bolster Preemption Defenses for Drug and Medical Device Manufacturers

On August 22, 2008, the FDA published a final rule in the Federal Register entitled "Supplemental Applications Proposing Labeling Changes for Approved Drugs, Biologics, and Medical Devices." The final rule modifies 21 CFR Parts 314, 601 and 814. The FDA's stated objective in promulgating the final rule is to codify the FDA's "longstanding view concerning when a change to the labeling of an approved drug, biologic, or medical device may be made in advance of the agency's review and approval of such change . . ." Specifically, the final rule addresses the supplemental application process for labeling changes of approved drugs, medical devices and biological products as described in §§ 314.70(c), 814.39(d) and 601.12(f)(2), which are commonly known as the "changes being effected (CBE) supplements."

Publication of the final rule follows a period of time for public comment after the FDA published the proposed rule on January 16, 2008, in the Federal Register. The FDA's authority to modify §§ 314.70, 601.12 and 814.39 is based upon the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 301 et seq., which enables the FDA to review and approve applications of label changes to drugs, medical devices and biological products. The final rule is effective as of September 22, 2008.

The final rule clarifies the FDA's pre-existing view of when a CBE supplement is appropriate. The FDA emphasizes that a CBE supplement should be used to amend the labeling of an approved drug, medical device or biologic product "only to reflect newly acquired information." In addition, the final rule explains that there must be "reasonable evidence of a causal association" before a CBE supplement "may be used to add or strengthen a contraindication, warning, precaution, or adverse reaction." While the FDA states that the final rule merely clarifies its interpretation of when drug, medical device or biologic product manufacturers are permitted to add or supplement information to their products' labeling in regard to risks associated with that product, the final rule has evident ramifications in products liability litigation insofar as the final rule provides drug manufacturers with additional support when asserting preemption defenses.

Preemption Defenses Buttressed by FDA's Final Rule

The final rule defines "newly acquired information" as "information not previously submitted to FDA." Inclusive within the definition of "newly acquired information" is information that the product manufacturer did not previously submit to the FDA. Within the definition of "newly acquired information" is also post-product approval data or analyses that demonstrate the product's prior warnings were insufficient. Furthermore, the definition of "newly acquired information" includes "new analyses of previously submitted information." Thus, reports of adverse events, data from new clinical studies, or new analyses of previously submitted data will be deemed "newly acquired information" if the newly discovered adverse events, results of clinical studies, or new analyses "reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA."

Under the final rule, however, a CBE supplement is available only if there is "sufficient evidence of a causal association" justifying the addition or strengthening of a contraindication, warning, precaution or adverse reaction. The FDA explains that the language "sufficient evidence of a causal association" refers to the standards for drugs and biologics set forth in §201.57(c)(6) and §201.57(c)(7). Under §201.57(c)(6), causation need not be "definitely established" to require inclusion of a warning on a label, but rather the standard for inclusion is that there be "reasonable" evidence of a causal association.

Prior to publication of the final rule, plaintiffs could argue with some success that the CBE supplement procedure allowed manufacturers to change their product's labeling in advance of FDA review and approval. In particular, plaintiffs could claim that state law imposed a duty on a manufacturer to change its product's label without FDA approval, which the manufacturer could accomplish via the CBE supplement method. The effect of the final rule, however, is to limit the scenarios in which manufacturers of drugs, biologics and medical devices can change a previously approved label in advance of the FDA's review and approval mechanism. In the context of products liability litigation, especially drug litigation, where plaintiffs allege that product manufacturers violated state law by failing to unilaterally include additional label warning(s), the final rule provides further clarification of the FDA's view on preemption in such situations. In particular, the FDA asserts in the final rule that when a product manufacturer "did not meet the standard to change its labeling through a CBE supplement under this rule to include the warning a plaintiff alleges should have been added to labeling, State law liability that is premised on a failure to warn is preempted." Therefore, any new or additional warning a plaintiff claims is required under state law will be preempted unless the specific alleged new or additional warning satisfies the new standard to change a label pursuant to the CBE supplement process as established by the FDA's final rule.