The Food and Drug Administration has finalized the updated rule on using supplemental applications for changes to prescription drug, biologics, and medical device labels. The final rule, 73 Fed. Reg. 49603, allows manufacturers to submit a supplemental application to amend the labeling for an approved product to reflect newly acquired information. These supplements are commonly referred to as “changes being effected supplements” or “CBE supplements.” The final rule becomes effective on Sept. 22, 2008. The final rule modifies 21 C.F.R. Sections 314, 601 and 814.

MassTortDefense would disagree with the media reports describing this as a “new” rule. In fact, the final rule affirms FDA’s longstanding position that a CBE supplement is appropriate to amend the labeling for an approved product only to reflect newly acquired information. But even though when it originally adopted this regulation FDA intended it as a limited, narrow, emergency exception to the general rule of Agency pre-approval of changes to prescription drug labeling, after preemption became a huge issue in prescription drug product liability litigation the regulation has been at times cited by courts as applying far more broadly than the FDA intended.

Plaintiffs argued that, since manufacturers are supposedly free to change their labels without prior FDA approval, there can be no conflict with state law holding them liable for not doing what the regulation supposedly allows. The plaintiffs thus have argued that the narrow exception swallows the rule that drug labeling changes are subject FDA pre-approval. Some courts have accepted this argument, and for example ruled that pharmaceutical defendants should have unilaterally strengthened suicide warnings for antidepressants – despite the FDA having evaluated the evidence of this alleged risk multiple times, concluding that there is no sufficient scientific basis for including a suicide warning. Compare McNellis v. Pfizer, Inc., 2006 WL 2819046 (D.N.J. Sept. 29, 2006) with Colacicco v. Apotex, Inc., 432 F. Supp.2d 514, 523, 527-28 (E.D. Pa. 2006). The Third Circuit’s  take on this split is at Colacicco v. Apotex, 521 F.3d 253 (3d Cir. 2008).

FDA proposed the CBE procedure in 1982, making clear at the time that CBE supplements were intended to apply only if the sponsor became aware of newly discovered safety information that was appropriate for inclusion in the labeling for the product. Since then, the FDA has repeatedly tried, through amicus briefs, and in the 2006 preemption preamble, to inform courts of the limited scope of the regulation, with arguably mixed success. In briefs recently filed in the Supreme Court and in testimony before Congress, FDA has also stated a more generally applicable rule that is consistent with the examples of  cases finding preemption, and the principles set forth in the preamble to the 2006 Physician Labeling Rule,  that: (1) The labeling requirements are not a mere minimum safety standard, but rather strike a balance between risks and benefits, and (2) FDA’s regulations permit changes in labeling without prior approval only in narrow circumstances. Specifically, FDA has explained that State law claims that “challenge labeling that FDA approved after being informed of the relevant risk” are preempted.

So now, the agency decided to change the regulation to say precisely what the agency has said it meant all along, with the hope that the lawyers and judges who have been ignoring it can’t do so any longer.

In January, several liberal Democrats in Congress wrote a letter to FDA questioning the basis for the proposed CBE rule, saying it appeared to be designed to shield pharmaceutical and medical device companies from liability sustained by consumers. But the rule does not alter the agency’s current practices with respect to accepting or rejecting labeling changes proposed by a CBE supplement, reiterating the agency’s longstanding view that the changes-being-effected mechanism is a narrow exception to the FDA’s requirement of prior approval for labeling changes to approved products.

Under the rule, newly acquired information means data, analyses, or other information not previously submitted to the agency, which may include (but are not limited to) data derived from new clinical studies, reports of adverse events, or new analyses of previously submitted data (e.g., meta-analyses) — if the studies, events or analyses reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA. The final rule thus clarifies the meaning of “newly acquired information,” such that the data, whether derived from new clinical studies, reports of adverse events, etc., needs to be new and different — of a different type or greater severity or frequency than previously submitted to FDA. This limitation applies to data derived from new clinical studies, reports of adverse events, and new analyses of previously submitted data, alike. The final rule notes thus 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 language.

The FDA rejected comments suggesting that a lower standard should be used under CBE for when a sponsor may warn, reiterating that it “interprets the 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.”

The new rule may be of some assistance in dealing with those courts that seem reluctant to recognize the longstanding view of the narrow scope of the CBE rule.  The rule limits the scenarios in which manufacturers of drugs, biologics, or medical devices can change a previously approved label in advance of the FDA’s formal review and approval mechanism. And the smaller the scope of things permitted in a CBE change, the greater the scope of conflict between FDA-approved labels and state court second-guessing of the warnings.