The U.S. Food and Drug Administration recently announced it will withdraw a proposed rule that would have required generic drug manufacturers to independently update their drug labels with new information. The proposed rule, Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products, would have imposed on generic drug manufacturers the same labeling-update mandates that now apply only to brand-name drug manufacturers.
Currently, generic drug manufacturers who hold an Abbreviated New Drug Application (ANDA) are barred from making unilateral changes to their labels unless the corresponding branded "reference listed drug" (RLD) manufacturer does so first. If the branded RLD manufacturer does make such a change, the generic ANDA holder must revise its own labeling "at the very earliest time possible." These procedures, instituted by the Hatch-Waxman Act's "sameness" requirement for generic drug labeling, would have been significantly upended by the enforcement of the proposed rule.
Under the proposed rule, an ANDA holder had to submit a Changes Being Effected-0 (CBE-0) supplement to their ANDA and its label, whenever it had "newly acquired information" that provided "sufficient evidence of a causal association" between an unlabeled warning and the generic drug. To ensure the prompt communication of these new warnings, the ANDA holder would then distribute a "Dear Health Care Provider" letter alerting physicians to the newly discovered hazard. Furthermore, the FDA also would have required that the changed labeling be submitted in the "structured product labeling" format, which allows the FDA to promptly place the new warnings online.
In addition to the rule's FDA reporting requirement, it obligated the generic ANDA holder to notify the branded RLD manufacturer in writing of the proposed labeling change. The information supporting the proposed labeling change would be included in the notice. The RLD manufacturer would, theoretically, use the information to either propose a matching change in its own labeling or comment on the change proposed by the ANDA holder. The FDA would then place the label change on a dedicated website for public review and access by other generic firms.
The rule also altered generic firms' timelines for labeling modifications. If the RLD manufacturer approved the proposed ANDA label change, the ANDA holder had 30 days to submit another CBE-0 supplement covering that change. To comply with the Hatch-Waxman sameness requirement, the FDA would then defer the official approval of the generic ANDA holder's initial change until the branded RLD manufacturer submitted and secured approval of its own change. The deferral ensured that the approved labeling for branded and generic drugs would never be different.
To fulfill these new reporting and labeling requirements, generic manufacturers would have needed to create costly new compliance systems or risk conflicting with the FDA and their new labeling responsibilities. These systems would have handled ongoing reporting duties for adverse events, with the added burden of analyzing the "newly acquired information" contemplated by the rule and evaluating whether that information triggered a need to add new warnings to a product's labeling. Manufacturers predicted that the new costs would significantly and adversely impact generic drug prices, a concern that FDA Commissioner Scott Gottlieb referenced when announcing the rule's withdrawal.
The rule also would have expressly done away with current preemption defenses for generic drug manufacturers. The United States Supreme Court established preemption defenses for generic drug manufacturers through its holdings in PLIVA v. Mensing in 2011 and Mutual Pharmaceutical v. Bartlett in 2013. Those rulings allowed generic firms to assert preemption defenses when confronted with failure-to-warn and design defect claims, respectively. These defenses recognize that generic manufacturers are caught between Hatch-Waxman's sameness requirement and FDA regulations that prevent them from unilaterally altering their labeling without RLD-holder action. If the FDA implemented the proposed rule, these defenses would become unavailable as generic manufacturers would have their own independent obligation to strengthen label warnings.
Ultimately, the FDA pulled the rule amid concerns from the generic manufacturing community. The FDA said that the rule may have caused brand name and generic drugs to temporarily have different warnings on their labels, which in turn may have sunk consumer confidence in generic drugs and their equivalents. The rule may also have exposed generic manufacturers to product liability lawsuits premised on a failure to timely warn physicians of adverse events, new science reported in professional literature or a reanalysis of post-market surveillance data. Although the FDA chose not to implement the final rule, FDA Commissioner Gottlieb clarified that the withdrawal "doesn't change the ongoing obligations under [the] FDA's current regulations for all brand-and generic-drug manufacturers."
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