FDA's proposal to restrict when companies can revise product labeling without first getting agency approval drew a sharp reaction from lawyers involved in product liability litigation.

Lawyers on both sides of these suits say the rule will strengthen FDA preemption, the claim by manufacturers that FDA labeling requirements preempt state tort claims that they failed to adequately warn of a product's risks.

In a proposed rule to revise its labeling regulations, FDA stated that companies can alter product labeling without prior FDA approval only when new safety information emerges. In addition, companies may strengthen contradictions and warnings "only if there is sufficient evidence of a causal association with the drug, biologic, or device."

While the agency said the revision, which was published in the Jan. 16 Federal Register, would not be a substantive change to its current policy, many lawyers disagreed.

"This will have a significant impact on product liability litigation," Jim Beck, counsel at Dechert, said in an interview. By limiting when companies can change labeling without FDA clearance, the rule limits "plaintiffs' best argument against preemption."

The American Association for Justice (formerly known as the Association of Trial Lawyers of America) demanded that FDA retract the proposed rule.

"The rule is going to allow drug companies to claim immunity at the outset," AAJ regulatory counsel Gerie Voss told "The Pink Sheet." "Companies will be able to file a motion to dismiss or motion for summary judgment before a patient gets to state the circumstances of their claims."

FDA said the proposed rule would "codify the agency's longstanding view" on when a labeling change can be made prior to FDA approval. Beck said the current labeling regulation is broad and vague and does not specify when companies can change labeling on their own. In product liability litigation plantiffs have argued that manufacturers can change labeling to strengthen a warning without prior clearance by the agency.

FDA has repeatedly refuted this position in amicus briefs supporting preemption. While the agency does not mention the term in the proposed rule, it reiterates arguments it has made before the courts.

"Allowing a sponsor, without prior FDA approval, to add information to the labeling for a product based solely on data previously submitted to the FDA would undermine FDA's approval process and could result in unnecessary or confusing information being placed in the labeling for a drug, biologic, or medical device," the proposed rule states.

The U.S. Department of Justice's Solicitor General has advocated for preemption in amicus briefs submitted to the U.S. Supreme Court in three cases. Most recently, in Wyeth v. Levine the Solicitor General argued that FDA regulation does not allow manufacturers to make unilateral label changes based on information that was previously available to the agency (¹ Also see "FDA Preemption Cases Expected To Stay On Top Of Legal Calendar In 2008" - Pink Sheet, 7 January, 2008., p. 20).

Solicitor General Paul Clement sent a letter to the Supreme Court on Jan. 16 notifying it of FDA's proposed rule. He said the rule "may be relevant" in the three cases pending before the court: Riegel v. Medtronic, Warner-Lambert v. Kent and Wyeth v. Levine.

Brian Wolfman, director of Public Citizen's litigation group and counsel to the plaintiff in the Wyeth suit, followed up with his own letter to the Supreme Court advising it not to take up the case.

The proposed rule "is an attempt to codify" the views of Wyeth and the Solicitor General by substantially altering FDA's labeling regulation, Wolfman wrote. "For three reasons, this eleventh-hour development underscores respondent's position that the petition in this case should be denied."

Wolfman said that while the rule would not affect the Levine case, the court should wait to address preemption until the administrative process is completed. He said FDA may revise the proposed rule in response to comments it receives.

FDA specifically requested the public to address when a safety issue associated with a drug, biologic or medical device should be considered newly acquired. It also invited comments from state and local officials since the proposed rule raises the issue of federalism. Comments are due within 60 days.

Companies submit labeling revisions in a supplemental new drug application, referred to as "changes being effected," or CBE, supplement. FDA says it proposed the current CBE procedure in 1982 specifying that such supplements were to be filed "only if the sponsor became aware of newly discovered safety information that was appropriate for inclusion in the labeling for the product."

The agency said it "intends to consider information 'newly acquired' if it consists of data, analyses, or other information not previously submitted to the agency, or submitted within a reasonable time period prior to the CBE supplement, that provides novel information about the product, such as a risk that is different in type or severity than previously known risks about the product."

For example, FDA said, if a postmarket study demonstrates that an approved product has a more severe risk of a significant adverse reaction than previously known, a CBE supplement may be appropriate. However, if data from a postmarket study is an accumulation of information previously submitted to the agency, a CBE supplement would not be appropriate.

FDA said it also "intends to consider significant new analyses of previously submitted data (e.g. meta-analyses) that provide novel information about the product to constitute newly acquired information." GlaxoSmithKline revised its Avandia (rosiglitazone) labeling after a meta-analysis of clinical trial data found that the diabetes pill may increase the risk of heart attack. However, the boxed warning states that data on the risk of myocardial ischemia are "inconclusive" (² Also see "Avandia Adds Black Box For Heart Attack Risk; Actos Launches Ads" - Pink Sheet, 19 November, 2007., p. 3).

FDA's proposed rule follows a legislative fight about preemption during the drafting of the Food and Drug Administration Amendments Act. Signed into law in September 2007, FDAAA gives FDA authority to initiate labeling changes for drugs when it becomes aware of new safety information. Language in the Senate version of the bill that was seen as creating a more direct preemption defense for firms was dropped, however, as was explicit anti-preemption language in the House version. Instead, a "rule of construction" was included stating that sponsors' obligations to maintain their labels have not changed (³ Also see "Pre-emption Limits Survive In Congress, Must Now Stare Down Supreme Court" - Pink Sheet, 24 September, 2007., p. 5).

The trial lawyers group contends that FDA is trying to get around the intent of the law. "If you read the FDAAA in conjunction with statements made on the floor by managers of the House and Senate, it's clear Congress intended to make sure drug companies maintained their own independent obligation to warn of the risk of a drug as soon as research showed evidence of a risk," Voss said.

- Brenda Sandburg (b.sandburg@elsevier.com)

FDA Preemption: Agency’s Proposed Labeling Rule Riles Plaintiffs’ Bar

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