On Friday, FDA announced a proposed rule* that, if finalized, will represent a significant change for generic drug companies. Section 505(j) of the Federal Food, Drug, and Cosmetic Act (FDCA) requires that, to be approved, generic drugs have the “same”** approved labeling as the brand-name drug (known as the reference listed drug, or RLD), and it has long been FDA’s position that this “same labeling” requirement applies throughout the life of the drug. But the proposed rule announced Friday would change that position by allowing generic drug companies to substantively update their drugs’ labeling, without waiting for the RLD’s labeling to be updated first, to reflect newly acquired information about the drug. This is big news not just because it would change generic drug companies’ obligations under FDA regulations, but also because of what this change may mean for generic drug companies’ tort liability.
Currently, the lay of the drug labeling land is as follows. Once a drug is approved – whether it is a brand-name RLD or a generic – the manufacturer may make changes to the FDA-approved labeling through three different types of submissions: (1) a prior approval supplement; (2) a changes-being-effected supplement (CBE), or; (3) an annual report. Changes submitted via a prior approval supplement, as the name implies, cannot be implemented until FDA approves the changes. Changes submitted via a CBE can be implemented upon FDA’s receipt of the supplement—although FDA still reviews and approves (or rejects) the proposed changes. Labeling changes described in the annual report are very minor changes, such as editorial revisions. An RLD’s labeling must be updated through the submission of a CBE to reflect newly acquired information to add or strengthen a warning about a clinical significant hazard as soon as there is reasonable evidence of a causal association (see 21 CFR 201.57(c)(6) and 314.70(c)). However, because of the “same labeling” requirement, the CBE process is only available for generic drugs when a generic drug’s labeling must be updated to match changes to the RLD’s approved labeling. In other words, a generic drug company cannot independently update its drug’s labeling to add or strengthen a warning before FDA approves an update to the RLD’s labeling.
It is this difference in access to the CBE process that underpins the Supreme Court’s decision that state law failure-to-warn claims are not preempted for brand-name RLDs (in Wyeth v. Levine), while such failure-to-warn claims, as well as design defect claims that turn on the adequacy of a warning, are preempted for generic drugs (in Pliva v. Mensing, and Mutual v. Bartlett, respectively). As the Supreme Court explained in Pliva, Federal law preempts state law “where it is impossible for a private party to comply with both state and federal requirements.” Because generic drug companies cannot independently update their drugs’ labeling via a CBE, generic drug companies cannot comply with state law requirements for adequate warnings without violating Federal requirements that a generic drug’s labeling match the RLD’s labeling. The Supreme Court, thus, has found that state law claims related to warnings on generic drugs’ labeling are preempted.
The proposed rule, however, would enable generic drug companies to independently update their drugs’ labeling, and, accordingly — as FDA acknowledges — it may eliminate preemption of these state law claims against generic drug companies. Indeed, I think the only reason that the proposed rule, if finalized, would not eliminate this preemption is if a final rule is challenged, and the courts find that the FDCA does not permit FDA to extend the CBE process to generic drugs. As noted above, section 505(j) of the FDCA requires that, to be approved, a generic drug have the same labeling as its RLD. One could argue that, consistent with FDA’s previous (and longstanding) interpretation, this language demonstrates Congress’ intent that generic drug companies’ not be permitted to independently update their drugs’ labeling.
This question may be the next big issue in generic drug tort litigation because it’s not clear, based on Pliva v. Mensing and Mutual v. Bartlett, whether the Supreme Court thinks legislative change is necessary to permit generic drug companies to independently update their drugs’ labeling. Some language in Pliva may suggest that FDA has the authority to change its regulations as it proposed to do on Friday (e.g., “it is also possible that, by asking, the [generic drug] Manufacturers could have persuaded the FDA to rewrite its generic drug regulations entirely . . .”), while some language in Mutual v. Bartlett may suggest legislative change is necessary to enact this proposal (e.g., “Congress’ decision to regulate the manufacture and sale of generic drugs in a way that reduces their cost to patients but leaves generic drug manufacturers incapable of modifying either the drugs’ compositions or their warnings . . .”). FDA, obviously, takes the position in the proposed rule that it has the statutory authority to extend the CBE process to generic drugs. But, perhaps unsurprisingly, there have already been media reports that the trade group for the generic drug industry questions whether the FDCA supports FDA’s interpretation.
In addition to this legal issue, the proposed rule raises some interesting public health policy questions (e.g., Would the proposal raise the cost of generics? If so, is any increased cost appropriate to help ensure that patients dispensed brand-name and generic drugs have equal access to the courts?). And I’ll be interested to see what comments FDA receives on the legal and policy questions. On that note, if you have an opinion on this proposed rule, you have 60 days from the date that the rule officially publishes in the Federal Register – scheduled for tomorrow, Nov. 13 – to submit comments to the agency.
*On Friday, FDA also responded to a Citizen Petition from Public Citizen requesting some of the changes proposed in the rule. The Citizen Petition, comments submitted about the Citizen Petition, and FDA’s response can be viewed here.
**There are a few exceptions to the general requirement that generic drugs have the same labeling as the brand-name RLD. For example, there may differences in the labeling that reflect the fact that the generic drug and the RLD have different manufacturers. See section 505(j)(2)(A)(v) of the FDCA.