Opinion ID: 70441
Heading Depth: 2
Heading Rank: 3

Heading: Dear Doctor Letters

Text: In addition to the CBE and prior approval processes, Demahy posits that Actavis could have satisfied its state-law duty to warn by communicating directly with doctors, through a Dear Doctor letter. These lettersaddressed to medical professionals and intended to explain the risks associated with prolonged use of metoclopramidewould also be subject to FDA regulation because they fall within the agency's broad definition of labeling. [106] But, when promulgating its labeling regulations well before the Hatch-Waxman Amendments, the FDA made clear that the requirements do not prohibit a manufacturer... from warning health care professionals whenever possibly harmful adverse effects associated with the use of the drug are discovered. [107] Thus, though generic manufacturers cannot send Dear Doctor letters without prior FDA approval, they can suggest that the FDA send such letters on their behalf; [108] the FDA will then send letters out if it determines that they are a necessary part of a risk evaluation and mitigation strategy. [109] Under Louisiana law, a drug manufacturer may discharge its duty to warn through notice to the prescribing physician. [110] Of the three avenues for complying with both state and federal law that Demahy identifiesthe CBE process, the prior approval process, and letters sent directly to healthcare providerseach shares the same fundamental attributes: the manufacturer bears primary responsibility for maintaining its label consistent with safe and effective use of its product; when reports indicate that a label requires revision, the manufacturer must alert the FDA and provide supporting scientific data; and the FDA then makes the decision whether such a labeling change is supported by science. Even though with the CBE process, the decision is made after the label has been changed, the key feature remains: the FDA is still the final arbiter of labeling changes, while the manufacturer retains primary responsibility for the content of its label. The federal interest is in maintaining safe and effective labeling that is consistent across name brand and generic bioequivalent versions of the same drug. Who prompts the FDA to consider necessary changes to that shared label is immaterial. At best, Actavis has demonstrated that even an interpretation of the CBE process most favorable to Actavis (and one that fails to persuade this court) is decidedly equivocal. Yet, equivocation falls short of the clear and manifest purpose of Congress required for a finding of preemption. [111] Even assuming that the CBE regulation cannot be used by an ANDA holder to amend its label without FDA pre-approval, Levine 's principles still apply with full force, and we agree with Demahy that generic drug manufacturers may use two other means of complying with both federal and state lawthe prior approval process and correspondence sent directly to healthcare providers. Though most courts to have considered the questionincluding the one below focus on the CBE process, the CBE regulation was not the exclusive, or even the primary, basis for rejecting preemption in Levine. Rather, the Court explained that the brand name drug manufacturer's quest for preemption was grounded in a more fundamental misunderstanding of the regulatory regime: that the FDA, rather than the manufacturer, bears primary responsibility for drug labeling. [112] As we have seen, the opposite is true: a central premise of federal drug regulation [is] that the manufacturer bears responsibility for the content of its label at all times. [113] Actavis urges that Congress intended to preempt state law because FDA regulations do not impose a duty on generic manufacturers to change their drug labels. This argument does not address the question we must answer. Preemption is not found because state law imposes duties and federal law does not. We look instead to the state-law imposition of duties, and to whether those duties make simultaneous compliance with federal law impossible. What the FDA might have done once Actavis suggested these changes is immaterial to the imposition of liability; Levine makes plain that uncertainty about the FDA's response makes federal preemption less likely: absent clear evidence that the FDA would not have approved a change to [the drug's] label, we will not conclude that it was impossible for the [the manufacturer] to comply with both federal and state requirements. [114] The record here contains nothing, let alone clear evidence, that suggests the FDA would have rejected a labeling proposal from Actavis. In fact, as discussed, the FDA mandated earlier this year that manufacturers of metoclopramide revise their labels to disclose further risks of tardive dyskinesia associated with long-term use. [115] Finally, Actavis's use of Justice Breyer's concurrence in Levine is here unavailing: he said if an agency sets a floor and a ceiling, its actions may very well enjoy preemptive effect. No such regulation bearing the force of law is before us, while the FDA's retreat from its earlier position on preemption and the use of the CBE provision casts further doubt on Actavis's argument. That being said, had the FDA gone further than Justice Breyer would require and specifically examined the risk of long-term use of metoclopramide at the time that Demahy's cause of action arose, the argument for preemption would be on surer footing. [116]