Opinion ID: 4231251
Heading Depth: 2
Heading Rank: 1

Heading: Federal Regulation of Drug Labeling

Text: The Food, Drug, and Cosmetic Act (FDCA; 21 U.S.C. § 301 et seq.) prohibits the marketing of a new brand-name drug unless the manufacturer has submitted a new drug application (NDA) and the Food and Drug Administration (FDA) has approved the drug as safe and effective for its intended use. (21 U.S.C. § 355(a).) The NDA must include an exemplar of the drug’s proposed label (21 U.S.C. § 355(b)(1)(F)) describing the drug’s indications and usage, 4 contraindications, warnings and precautions, and adverse reactions. (21 C.F.R. § 201.56(e)(1).) In 1984, Congress enacted the Hatch-Waxman Act. (98 Stat. 1585, 15851597, codified as amended at 21 U.S.C. § 355.) This statute allows a prospective generic drug manufacturer to file an abbreviated new drug application (ANDA) asserting the generic drug’s bioequivalence to an existing listed drug that has already been approved by the FDA. (PLIVA, Inc. v. Mensing (2011) 564 U.S. 604, 612 (PLIVA), citing 21 U.S.C. § 355(j).) Such an application is typically filed as the brand-name drug’s patent is about to expire. The streamlined application relieves the generic manufacturer of the need to duplicate the clinical trials previously submitted for the equivalent brand-name drug. (Ibid.) The generic manufacturer must nonetheless “show that the labeling proposed for the new drug is the same as the labeling approved for the listed drug.” (21 U.S.C. § 355(j)(2)(A)(v).) So under the federal scheme, “brand-name and generic drug manufacturers have different federal drug labeling duties.” (PLIVA, supra, 564 U.S. at p. 613.) It is the brand-name manufacturer that bears responsibility for the accuracy and adequacy of its label “as long as the drug is on the market.” (Wyeth v. Levine (2009) 555 U.S. 555, 570-571 (Wyeth).) The generic manufacturer, on the other hand, is responsible only for “an ongoing federal duty of ‘sameness’ ” — that is, ensuring that its warning label is the same as the brand-name manufacturer’s. (PLIVA, at p. 613.) FDA regulations require the brand-name drug manufacturer to update the warning label “as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.” (21 C.F.R. § 201.80(e); cf. id., § 314.80(b) [NDA holder “must promptly review all adverse drug experience information obtained or otherwise received by the 5 applicant from any source”].) A specific warning is required if the drug is commonly prescribed for a disease or condition, even when the drug has not yet been approved for that use, where “such usage is associated with serious risk or hazard.” (Id., § 201.80(e).) Any manufacturer of the drug at issue may request a change in the label by submitting a “prior approval supplement” to the FDA, which decides whether to approve the requested change in the warning label. (21 C.F.R. § 314.70(b)(2)(v); FDA, Abbreviated New Drug Application Regulations, 57 Fed.Reg. 17950, 17961 (Apr. 28, 1992).) But a brand-name drug manufacturer, unlike a generic manufacturer, may unilaterally update a label, without waiting for FDA preapproval, “[t]o add or strengthen a contraindication, warning, precaution, or adverse reaction” under the “changes being effected” (CBE-0) regulation. (21 C.F.R. § 314.70(c)(6)(iii)(A); see Wyeth, supra, 555 U.S. at p. 568.) By contrast, a generic manufacturer may use the CBE-0 regulation only to conform its label to an updated brand-name label. (PLIVA, supra, 564 U.S. at p. 614.) Because federal regulations preclude generic manufacturers from unilaterally altering the warning labels on their drugs (PLIVA, supra, 564 U.S. at p. 617), federal law preempts state tort claims against generic manufacturers for failure to provide adequate warnings. (Id. at p. 609.) State tort claims against a brand-name manufacturer based on a failure to warn, however, are not preempted. (Id. at p. 625.)