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In 2007, after Levine’s injury and lawsuit, Congress again amended the FDCA. 121 Stat. 823. For the first time, it granted the FDA statutory authority to require a manufacturer to change its drug label based on safety information that becomes available after a drug’s initial approval. §901(a), id., at 924–926. In doing so, however, Congress did not enact a provision in the Senate bill that would have required the FDA to preapprove all changes to drug labels. See S. 1082, 110th Cong., 1st Sess., §208, pp. 107–114 (2007) (as passed) (proposing new §506D). Instead, it adopted a rule of construction to make it clear that manufacturers remain responsible for updating their labels. See 121 Stat. 925–926.

III

Wyeth first argues that Levine’s state-law claims are pre-empted because it is impossible for it to comply with both the state-law duties underlying those claims and its federal labeling duties. See De la Cuesta, 458 U. S., at 153. The FDA’s premarket approval of a new drug application includes the approval of the exact text in the proposed label. See 21 U. S. C. §355; 21 CFR §314.105(b) (2008). Generally speaking, a manufacturer may only change a drug label after the FDA approves a supplemental application. 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. §§314.70(c)(6)(iii)(A), (C).

Wyeth argues that the CBE regulation is not implicated in this case because a 2008 amendment provides that a manufacturer may only change its label “to reflect newly acquired information.” 73 Fed. Reg. 49609. Resting on this language (which Wyeth argues simply reaffirmed the interpretation of the regulation in effect when this case was tried), Wyeth contends that it could have changed Phenergan’s label only in response to new information that the FDA had not considered. And it maintains that Levine has not pointed to any such information concerning the risks of IV-push administration. Thus, Wyeth insists, it was impossible for it to discharge its state-law obligation to provide a stronger warning about IV-push administration without violating federal law. Wyeth’s argument misapprehends both the federal drug regulatory scheme and its burden in establishing a pre-emption defense.

We need not decide whether the 2008 CBE regulation is consistent with the FDCA and the previous version of the regulation, as Wyeth and the United States urge, because Wyeth could have revised Phenergan’s label even in accordance with the amended regulation. As the FDA explained in its notice of the final rule, “ ‘newly acquired information’ ” is not limited to new data, but also encompasses “new analyses of previously submitted data.” Id., at 49604. The rule accounts for the fact that risk information accumulates over time and that the same data may take on a different meaning in light of subsequent developments: “[I]f the sponsor submits adverse event information to FDA, and then later conducts a new analysis of data showing risks of a different type or of greater severity or frequency than did reports previously submitted to FDA, the sponsor meets the requirement for ‘newly acquired information.’ ” Id., at 49607; see also id., at 49606.

The record is limited concerning what newly acquired information Wyeth had or should have had about the risks of IV-push administration of Phenergan because Wyeth did not argue before the trial court that such information was required for a CBE labeling change. Levine did, however, present evidence of at least 20 incidents prior to her injury in which a Phenergan injection resulted in gangrene and an amputation. See App. 74, 252.4 After the first such incident came to Wyeth’s attention in 1967, it notified the FDA and worked with the agency to change Phenergan’s label. In later years, as amputations continued to occur, Wyeth could have analyzed the accumulating data and added a stronger warning about IV-push administration of the drug.

Wyeth argues that if it had unilaterally added such a warning, it would have violated federal law governing unauthorized distribution and misbranding. Its argument that a change in Phenergan’s labeling would have subjected it to liability for unauthorized distribution rests on the assumption that this labeling change would have rendered Phenergan a new drug lacking an effective application. But strengthening the warning about IV-push administration would not have made Phenergan a new drug. See 21 U. S. C. §321(p)(1) (defining “new drug”); 21 CFR §310.3(h). Nor would this warning have rendered Phenergan misbranded. The FDCA does not provide that a drug is misbranded simply because the manufacturer has altered an FDA-approved label; instead, the misbranding provision focuses on the substance of the label and, among other things, proscribes labels that fail to include “adequate warnings.” 21 U. S. C. §352(f). Moreover, because the statute contemplates that federal juries will resolve most misbranding claims, the FDA’s belief that a drug is misbranded is not conclusive. See §§331, 332, 334(a)–(b). And the very idea that the FDA would bring an enforcement action against a manufacturer for strengthening a warning pursuant to the CBE regulation is difficult to accept—neither Wyeth nor the United States has identified a case in which the FDA has done so.

Wyeth’s cramped reading of the CBE regulation and its broad reading of the FDCA’s misbranding and unauthorized distribution provisions are premised on a more fundamental misunderstanding. Wyeth suggests that the FDA, rather than the manufacturer, bears primary responsibility for drug labeling. Yet through many amendments to the FDCA and to FDA regulations, it has remained a central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times. It is charged both with crafting an adequate label and with ensuring that its warnings remain adequate as long as the drug is on the market. See, e.g., 21 CFR §201.80(e) (requiring a manufacturer to revise its label “to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug”);§314.80(b) (placing responsibility for postmarketing surveillance on the manufacturer); 73 Fed. Reg. 49605 (“Manufacturers continue to have a responsibility under Federal law … to maintain their labeling and update the labeling with new safety information”).

Indeed, prior to 2007, the FDA lacked the authority to order manufacturers to revise their labels. See 121 Stat. 924–926. When Congress granted the FDA this authority, it reaffirmed the manufacturer’s obligations and referred specifically to the CBE regulation, which both reflects the manufacturer’s ultimate responsibility for its label and provides a mechanism for adding safety information to the label prior to FDA approval. See id., at 925–926(stating that a manufacturer retains the responsibility “to maintain its label in accordance with existing requirements, including subpart B of part 201 and sections 314.70 and 601.12 of title 21, Code of Federal Regulations (or any successor regulations)” (emphasis added)). Thus, when the risk of gangrene from IV-push injection of Phenergan became apparent, Wyeth had a duty to provide a warning that adequately described that risk, and the CBE regulation permitted it to provide such a warning before receiving the FDA’s approval.

Of course, the FDA retains authority to reject labeling changes made pursuant to the CBE regulation in its review of the manufacturer’s supplemental application, just as it retains such authority in reviewing all supplemental applications. But absent clear evidence that the FDA would not have approved a change to Phenergan’s label, we will not conclude that it was impossible for Wyeth to comply with both federal and state requirements.

Wyeth has offered no such evidence. It does not argue that it attempted to give the kind of warning required by the Vermont jury but was prohibited from doing so by the FDA. See Tr. of Oral Arg. 12–13; see also Brief for United States as Amicus Curiae 25. And while it does suggest that the FDA intended to prohibit it from strengthening the warning about IV-push administration because the agency deemed such a warning inappropriate in reviewing Phenergan’s drug applications, both the trial court and the Vermont Supreme Court rejected this account as a matter of fact. In its decision on Wyeth’s motion for judgment as a matter of law, the trial court found “no evidence in this record that either the FDA or the manufacturer gave more than passing attention to the issue of” IV-push versus IV-drip administration. App. 249. The Vermont Supreme Court likewise concluded that the FDA had not made an affirmative decision to preserve the IV-push method or intended to prohibit Wyeth from strengthening its warning about IV-push administration. ___ Vt., at ___, 944 A. 2d, at 188–189. Moreover, Wyeth does not argue that it supplied the FDA with an evaluation or analysis concerning the specific dangers posed by the IV-push method.We accordingly cannot credit Wyeth’s contention that the FDA would have prevented it from adding a stronger warning about the IV-push method of intravenous administration.6

Impossibility pre-emption is a demanding defense. On the record before us, Wyeth has failed to demonstrate that it was impossible for it to comply with both federal and state requirements. The CBE regulation permitted Wyeth to unilaterally strengthen its warning, and the mere fact that the FDA approved Phenergan’s label does not establish that it would have prohibited such a change.

IV

Wyeth also argues that requiring it to comply with a state-law duty to provide a stronger warning about IV-push administration would obstruct the purposes and objectives of federal drug labeling regulation. Levine’s tort claims, it maintains, are pre-empted because they interfere with “Congress’s purpose to entrust an expert agency to make drug labeling decisions that strike a balance between competing objectives.” Brief for Petitioner 46. We find no merit in this argument, which relies on an untenable interpretation of congressional intent and an overbroad view of an agency’s power to pre-empt state law.

Wyeth contends that the FDCA establishes both a floor and a ceiling for drug regulation: Once the FDA has approved a drug’s label, a state-law verdict may not deem the label inadequate, regardless of whether there is any evidence that the FDA has considered the stronger warning at issue. The most glaring problem with this argument is that all evidence of Congress’ purposes is to the contrary. Building on its 1906 Act, Congress enacted the FDCA to bolster consumer protection against harmful products. See Kordel v. United States, 335 U. S. 345, 349 (1948) ; United States v. Sullivan, 332 U. S. 689, 696 (1948) . Congress did not provide a federal remedy for consumers harmed by unsafe or ineffective drugs in the 1938 statute or in any subsequent amendment. Evidently, it determined that widely available state rights of action provided appropriate relief for injured consumers.7 It may also have recognized that state-law remedies further consumer protection by motivating manufacturers to produce safe and effective drugs and to give adequate warnings.

If Congress thought state-law suits posed an obstacle to its objectives, it surely would have enacted an express pre-emption provision at some point during the FDCA’s 70-year history. But despite its 1976 enactment of an express pre-emption provision for medical devices, see §521, 90 Stat. 574 (codified at 21 U. S. C. §360k(a)), Congress has not enacted such a provision for prescription drugs.See Riegel, 552 U. S., at ___ (slip op., at 14)(“Congress could have applied the pre-emption clause to the entire FDCA. It did not do so, but instead wrote a pre-emption clause that applies only to medical devices”).8 Its silence on the issue, coupled with its certain awareness of the prevalence of state tort litigation, is powerful evidence that Congress did not intend FDA oversight to be the exclusive means of ensuring drug safety and effectiveness. As Justice O’Connor explained in her opinion for a unanimous Court: “The case for federal pre-emption is particularly weak where Congress has indicated its awareness of the operation of state law in a field of federal interest, and has nonetheless decided to stand by both concepts and to tolerate whatever tension there [is] between them.” Bonito Boats, Inc. v. Thunder Craft Boats, Inc., 489 U. S. 141, 166–167 (1989) (internal quotation marks omitted); see also supra,at 8 (discussing the presumption against pre-emption).

Despite this evidence that Congress did not regard state tort litigation as an obstacle to achieving its purposes, Wyeth nonetheless maintains that, because the FDCA requires the FDA to determine that a drug is safe and effective under the conditions set forth in its labeling, the agency must be presumed to have performed a precise balancing of risks and benefits and to have established a specific labeling standard that leaves no room for different state-law judgments. In advancing this argument, Wyeth relies not on any statement by Congress, but instead on the preamble to a 2006 FDA regulation governing the content and format of prescription drug labels. See Brief for Petitioner 8, 11, 42, 45, and 50 (citing 71Fed. Reg. 3922 (2006)). In that preamble, the FDA declared that the FDCA establishes “both a ‘floor’ and a ‘ceiling,’ ” so that “FDA approval of labeling … preempts conflicting or contrary State law.” Id., at 3934–3935. It further stated that certain state-law actions, such as those involving failure-to-warn claims, “threaten FDA’s statutorily prescribed role as the expert Federal agency responsible for evaluating and regulating drugs.” Id., at 3935.

This Court has recognized that an agency regulation with the force of law can pre-empt conflicting state requirements. See, e.g., Geier v. American Honda Motor Co., 529 U. S. 861 (2000) ; Hillsborough County v. Automated Medical Laboratories, Inc., 471 U. S. 707, 713 (1985) . In such cases, the Court has performed its own conflict determination, relying on the substance of state and federal law and not on agency proclamations of pre-emption. We are faced with no such regulation in this case, but rather with an agency’s mere assertion that state law is an obstacle to achieving its statutory objectives. Because Congress has not authorized the FDA to pre-empt state law directly, cf. 21 U. S. C. §360k (authorizing the FDA to determine the scope of the Medical Devices Amendments’ pre-emption clause),9 the question is what weight we should accord the FDA’s opinion.

In prior cases, we have given “some weight” to an agency’s views about the impact of tort law on federal objectives when “the subject matter is technica[l] and the relevant history and background are complex and extensive.” Geier, 529 U. S., at 883. Even in such cases, however, we have not deferred to an agency’s conclusion that state law is pre-empted. Rather, we have attended to an agency’s explanation of how state law affects the regulatory scheme. While agencies have no special authority to pronounce on pre-emption absent delegation by Congress, they do have a unique understanding of the statutes they administer and an attendant ability to make informed determinations about how state requirements may pose an “obstacle to the accomplishment and execution of the full purposes and objectives of Congress.” Hines, 312 U.S, at 67; see Geier, 529 U. S., at 883; Lohr, 518 U. S., at 495–496. The weight we accord the agency’s explanation of state law’s impact on the federal scheme depends on its thoroughness, consistency, and persuasiveness. Cf. United States v. Mead Corp., 533 U. S. 218, 234–235 (2001) ; Skidmore v. Swift & Co., 323 U. S. 134, 140 (1944) .

Under this standard, the FDA’s 2006 preamble does not merit deference. When the FDA issued its notice of proposed rulemaking in December 2000, it explained that the rule would “not contain policies that have federalism implications or that preempt State law.” 65 Fed. Reg. 81103; see also 71 id., at 3969 (noting that the “proposed rule did not propose to preempt state law”). In 2006, the agency finalized the rule and, without offering States or other interested parties notice or opportunity for comment, articulated a sweeping position on the FDCA’s pre-emptive effect in the regulatory preamble. The agency’s views on state law are inherently suspect in light of this procedural failure.
Further, the preamble is at odds with what evidence we have of Congress’ purposes, and it reverses the FDA’s own longstanding position without providing a reasoned explanation, including any discussion of how state law has interfered with the FDA’s regulation of drug labeling during decades of coexistence. The FDA’s 2006 position plainly does not reflect the agency’s own view at all times relevant to this litigation. Not once prior to Levine’s injury did the FDA suggest that state tort law stood as an obstacle to its statutory mission. To the contrary, it cast federal labeling standards as a floor upon which States could build and repeatedly disclaimed any attempt to pre-empt failure-to-warn claims. For instance, in 1998, the FDA stated that it did “not believe that the evolution of state tort law [would] cause the development of standards that would be at odds with the agency’s regulations.” 63 id., at 66384. It further noted that, in establishing “minimal standards” for drug labels, it did not intend “to preclude the states from imposing additional labeling requirements.” Ibid.10
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