Too good to last? Will the FDA's proposed rule put an end to generic drug preemption under Mensing and Bartlett?

• Author: Diab, Tony M.

UNDER Mensing and Bartlett, state law generic drug product liability claims sounding in failure to warn are currently preempted. Simply put, because generic drug manufacturers cannot simultaneously comply with federal drug labeling regulations and state failure to warn laws, the state laws give way. A proposed FDA rule, however, may soon put an end to preemption of claims arising out of generic drug labels.

On November 13, 2013, the Food and Drug Administration ("FDA") proposed a rule that would reestablish failure to warn liability for generic drug manufacturers. The proposed rule would allow generic drug manufacturers to participate in the "changes being effected" ("CBE") process, thereby closing the gap between PLIVA, Inc. v. Mensing (1) and Wyeth v. Levine. (2) In Mensing, the Supreme Court held failure to warn claims against generic drug manufacturers preempted as a result of the duty of sameness applicable to generic drug labels based on the abbreviated new drug application ("ANDA") regulations. In essence, generic drug manufacturers are required to use the same language as in the warning labels of the reference listed drug ("RLD") identified by the FDA (generally, the brand-name drug). (3) This decision was strengthened by Mutual Pharmaceutical Company v. Bartlett, (4) which extended Mensing to cover design defect claims against generic drug manufacturers.

In Wyeth, the Supreme Court found that the CBE process, which allows brand drug manufacturers the ability to unilaterally change a drug's label pending FDA review of a proposed labeling change, precluded a finding of preemption in the context of failure to warn claims. (5) The Supreme Court reasoned that brand drug manufacturers were not bound by federal law to promulgate a defective warning label, but rather had the ability to alter a warning label to comply with the state law requirements by using the CBE process. (6)

The FDA's proposed rule seeks to close the gap between Mensing/Bartlett and Wyeth by including ANDA holders (generic drug manufacturers) in the CBE process--essentially imposing increased obligations on the generic manufacturers. Such a rule, however, may run afoul of the duty of sameness required by the ANDA process as set forth in Hatch-Waxman Amendments, (7) and thus lies beyond the power of the FDA. This article analyzes the FDA's attempt to undermine Mensing and Bartlett and whether such an effort is likely to succeed.

1. Wyeth v. Levine

   The Supreme Court first reviewed the question of federal preemption of state law failure to warn claims in Wyeth v. Levine. (8) There, the question presented was whether state law failure to warn claims were preempted by a drug manufacturer's duty to use only the FDA-approved warning label. (9)

   On April 7, 2000, Diane Levine received an injectable form of Demerol and Phenergan from her physician as treatment for migraine headaches. (10) Levine returned for a second treatment that same day, and "[t]his time, the physician assistant administered the drugs by the IV-push method, and Phenergan entered Levine's artery, either because the needle penetrated an artery directly or because the drug escaped from the vein into surrounding tissue [] where it came in contact with arterial blood. " (11) Levine's arm became infected and would have to be amputated. (12) Levine filed suit against Wyeth, alleging the warning label accompanying Phenergan did not warn of the risks of IV-push administration of Phenergan. (13)

   Prior to trial, Wyeth moved for summary judgment, arguing both express and implied preemption. (14) The trial court rejected both arguments, finding that Wyeth had made no effort to strengthen its warnings post-approval, which it was permitted to do under FDA regulations (i.e., the CBE process). (15) The evidence presented at trial showed that risks associated with the IV-drip method were substantially lower than that of the IV-push method. (16) The evidence also showed that while the Phenergan label warned against use of intra-arterial injection, it "did not contain a specific warning about the risks of IV-push administration." (17)

   In addition, evidence was presented showing Wyeth's compliance with the FDA regulations. (18) This included not only evidence that Phenergan's labeling at the time of Levine's injuries matched the FDA-approved label, but also correspondence between Wyeth and the FDA regarding the label for Phenergan. (19) The trial court instructed the jury, however, that although it could consider Wyeth's compliance with FDA requirements, such compliance did not establish that Wyeth's warning label was adequate. (20) The trial court further instructed the jury that "FDA regulations permit a drug manufacturer to change a product label to add or strengthen a warning about its product without prior FDA approval so long as it later submits the revised warning for review and approval." (21)

   The jury returned a verdict for Levine after finding Wyeth negligent and the warning label on Phenergan inadequate. (22) Wyeth moved for judgment as a matter of law on the basis of preemption, which the trial court denied. The trial court found that there was no direct conflict between FDA regulations and duties arising from state failure-to-warn laws because FDA regulations permit strengthened warnings without FDA approval through the CBE process. (23) The Vermont Supreme Court affirmed relying on the same reasoning. (24)

   Wyeth appealed the decision of the Vermont Supreme Court, arguing that it was impossible to comply with the state-law duty to modify Phenergan's labeling without violating federal labeling regulations. (25) Wyeth abandoned any argument of express preemption. (26) The United States Supreme Court granted review and affirmed.

   Wyeth argued, as it did before the courts below, that federal labeling regulations prohibit unilateral changes to an FDA-approved warning label. (27) Wyeth relied on federal statues, 21 U.S.C. [section] 355, and FDA regulations implementing such statutes, 21 C.F.R. 314.105(b). (28) The Supreme Court disagreed, relying on the CBE process, just as the courts below had done:

   There is, however, an FDA regulation that permits a manufacturer to make certain changes to its label before receiving the agency's approval. Among other things, this "changes being effected" (CBE) regulation provides that if a manufacturer is changing a label to "add or strengthen a contraindication, warning, precaution, or adverse reaction" or to "add or strengthen an instruction about dosage and administration that is intended to increase the safe use of the drug product," it may make the labeling change upon filing its supplemental application with the FDA; it need not wait for FDA approval. (29) The Supreme Court went on to explain the CBE process, which permits changes not only upon the discovery of new information, but also "new analyses of previously submitted data." (30) Thus, the Court rejected the argument that correspondence between Wyeth and the FDA showed that the risks of IV-push administration were known prior to the approval of Phenergan's warning label. (31)

   The Supreme Court left open the possibility of preemption for brand drug manufacturers, suggesting that "clear evidence that the FDA would not have approved a change to Phenergan's label" may support a conclusion of impossibility preemption. (32) The Court held Wyeth had offered no such evidence, but failed to indicate precisely what would constitute such "clear evidence." (33) No case since Wyeth has clarified the boundaries of this possible avenue for preemption for brand-name drugs.

   The Supreme Court also rejected field preemption, finding there was no indication that Congress had sought to set both a ceiling and floor with regard to drug labeling. (34) The Court noted that Congress could have chosen express preemption, as it did in the context of medical devices, and further that all indications in the legislative history suggest Congress did not seek to displace state law regulation of drugs. (35)

2. PLIVA, Inc. v. Mensing

   Two years later, in PLIVA, Inc. v. Mensing, the Supreme Court again addressed preemption, but this time in the context of generic drugs only. Mensing was a consolidated appeal of two different Court of Appeal decisions, Mensing v. Wyeth, (36) and Demahy v. Actavis. (37)

   Gladys Mensing was prescribed Reglan in 2001 to treat diabetic gastroparesis. (38) Mensing's pharmacist filled the prescription with generic metoclopramide, as permitted by Minnesota law, the law applicable to Mensing's claims. (39) Mensing consumed metoclopramide for four years, at which time she developed tradive dyskinesia, "a severe neurological movement disorder." (40) Generic defendants filed a motion to dismiss on the basis of preemption, which the trial court granted. The trial court reasoned that all of Mensing's claims sounded in failure to warn, and then held "Mensing's failure to warn claims created an impermissible conflict with federal law because they would require generic manufacturers to deviate from the name brand drug label." (41)

   On appeal, the Eighth Circuit reversed, concluding that "there is nothing in the [Food, Drug, and Cosmetic Act] or Hatch-Waxman Amendments that explicitly forbid [generic drug manufacturers] from proposing a label change." (42)

   Julie Demahy similarly was prescribed Reglan, but had her prescriptions filled with generic metoclopramide for a period of four years, at which point she too developed tardive dyskinesia...