Update on Pre-emption in Pharmaceutical Product Liability Cases

01 June 2007

Chilton Davis Varner, Stephen B Devereaux and Meredith A Bunn, King & Spalding LLP

In what is known as the ‘preemption preamble’, the FDA expressed its “long-standing view” that “under existing pre-emption principles, its approval of labelling under the [Food, Drug and Cosmetic Act. . . ] pre-empts conflicting or contrary State law” (Requirements on Content and Format of Labelling for Human Prescription Drug and Biological Products, 71 Fed Reg 3922, 3934, 2006). Seizing upon this language, pharmaceutical manufacturers are raising the pre-emption defence with increasing frequency − but with mixed results. Cases in which defendants have relied upon the Preamble are now starting to reach the federal appellate courts. The United States Court of Appeals for the third circuit, which is currently presiding over such a case (Colacicco v Apotex Inc), is likely to be the first to address pre-emption in the ‘post-preamble’ era.

The Role of The FDA

The FDA has congressional authority to implement regulations under and enforce the Food, Drug and Cosmetic Act (FDCA). The agency is charged with regulating the manufacture, sale and labelling of prescription drugs and ensuring that drugs sold in the US are safe and effective. As such, Congress authorised FDA to apply its scientific and regulatory expertise to determine what warnings are appropriate for prescription drugs.

As part of the new drug approval process, manufacturers must submit reports of investigations establishing that the drug is safe and effective for use under “the conditions prescribed, recommended, or suggested in the proposed labelling thereof ” (21 USC section 355d.1). When approving a new drug, the FDA also approves the precise final version of the drug labelling. The Act requires refusal of a new drug application if the labelling is false or misleading in any particular. Manufacturers also have a continuing obligation to submit investigation results, and any proposed labelling modifications must be evaluated and approved by the FDA.

The Pre-Emption Defence

Because of the FDA’s unique and pervasive role in regulating prescription drugs, the question of whether states have the power to impose additional (and often conflicting) labelling requirements on pharmaceutical manufacturers has often been raised in pharmaceutical product liability cases. There is a distinction between ‘express’ and ‘implied’ pre-emption. Express pre-emption is when Congress states in a statute that a certain type of claim is pre-empted by federal law.

Implied pre-emption (sometimes called ‘conflict’ preemption) is when Congress has said nothing one way or the other, but a particular state law may appear to conflict with federal law. In some instances, manufacturers have argued that, in the 1962 Kefauver Amendments to the FDCA, Congress expressed its intent to pre-empt state law in conflict with FDA’s prescription drug labelling authority. However, courts have generally taken the position that the FDCA does not contain such an express pre-emption provision. Implied pre-emption has been invoked more often and with more success, especially over the past six years (see, eg, Ehlis v Shire Richwood Inc, 233 F Supp 2d 1189, 1198 DND, 2002). The resurgence of this defence is due in part to the FDA’s concerted effort, since 2002, to publicise its views on conflict pre-emption. In a series of cases, the FDA provided amicus curiae support for pharmaceutical manufacturers in cases involving conflict pre-emption challenges to failureto- warn claims. Each time, it asserted that once the agency has determined what were the appropriate warnings, state law could not impose a more stringent labelling obligation (see, eg, Motus v Pfizer Inc, ninth circuit, filed 3 September 2002; Kallas v Pfizer Inc, D Utah, filed 15 September, 2005; Bernhardt v Pfizer Inc, SDNY, filed 13 November 2000). Despite the FDA’s involvement, not all courts have been receptive to the pre-emption defence (compare Needleman v Pfizer Inc, No. Civ A 3:03-CV-3074-N, 2004 WL 1773697, ND Tex 6 August, 2004 – relying on the FDA’s Motus amicus brief and finding pre-emption – with Witczak v Pfizer Inc, 377 F Supp 2d 726, 728-30, D Minn 2005 – finding no conflict between FDA requirements and state law).

Pharmaceutical manufacturers saw the FDA’s recent rulemaking, concerning proposed changes to the labelling regulations applicable to prescription drugs, as an opportunity to address the growing conflict in the courts. Manufacturers called on the FDA to state affirmatively whether its approval of labelling pre-empts conflicting state law for the purposes of product liability litigation. As noted above, in January of 2006, the FDA responded with the ‘preamble’ (Requirements on Content and Format of Labelling for Human Prescription Drug and Biological Products, 71 Fed Reg 3922, 3933-34, 2006). In issuing the new rule, it identified several categories of pre-empted claims, two of which are particularly relevant in the product liability context: claims that a manufacturer should not have made FDA-approved warnings and claims that a manufacturer should have provided additional warnings not approved by the FDA.

Colacicco v Apotex Inc

The pre-emption preamble may have shifted the balance in favour of pre-emption. Although there is not yet a consensus among the courts that have addressed pre-emption since January 2006, the emerging trend is to embrace the FDA position on pre-emption of failure-to-warn claims.

The leading federal case finding pre-emption is Colacicco v Apotex Inc, 432 F Supp 2d 514 (ED Pa 2006). Colacicco offers an illustrative window into the pharmaceutical preemption debate, drawing the issue in a sharply defined way. This case is currently on appeal to the US Court of Appeals for the third circuit and has been consolidated with McNellis v Pfizer Inc, No. 05-1286 JBS, 2005 WL 3752269 (DNJ 29 December 2005), a similar case that reached the opposite conclusion.

In Colacicco, the plaintiff alleged that the defendants, Apotex Inc and GlaxoSmithKline (GSK), failed to warn of the increased risk of suicidal behaviour linked to Paxil and its generic equivalent, which allegedly resulted in the suicide of the plaintiff ’s wife. The defendants moved to dismiss the case, arguing that FDA’s authority over prescription pharmaceuticals pre-empted the plaintiff ’s claims. At the court’s request, the FDA filed an amicus brief in which it argued that pre-emption did apply, consistent with the preamble.

The district court agreed with the defendants and the FDA. In so doing, the court determined that considerable deference was due to the FDA’s pre-emption position, both as expressed in the preamble and the amicus brief. The court emphasised that “it is not the function of this Court, or for a jury empanelled to decide this case, to substitute its judgment for the FDA’s about these medical issues” (Colacicco, 432 F Supp 2d at 530).

On appeal, Colacicco asserted three major arguments in favour of reversing the district court: a presumption against preemption; that no deference is due to the FDA’s statement of pre-emption; and that FDA regulation and state law do not directly conflict. According to Colacicco, every preemption analysis starts from the assumption that Congress did not intend for state law to be pre-empted. Colacicco contends that the district court improperly ignored the ‘presumption against pre-emption’ and instead improperly placed emphasis on FDA’s intent.

In response to this line of attack, the defendants argued that the presumption applies only in fields that are traditionally regulated by the states. As the defendants pointed out, states have never regulated prescription-drug labelling. Rather, such regulation is uniquely federal in nature because of the compelling need for national uniformity. As such, the defendants argue that no presumption against pre-emption applies in these circumstances.

Colacicco next contended that FDA’s view on pre-emption expressed in the preamble and numerous amicus briefs is not entitled to deference. Courts generally give deference to an agency’s interpretation of the statute and regulations it administers. In Geier v American Honda Motor Co, 529 US 861 (2000), for example, the Supreme Court made clear that agency interpretations of the pre-emptive effect of their regulating activities presented in amicus briefs as well as regulations, preambles, interpretive statements, and responses to comments are entitled to deference. Colacicco maintained, however, that the ‘Pre-emption Preamble’ should be disregarded for several reasons. To begin with, while FDA’s interpretations of medical issues might be entitled to deference, whether its regulations have pre-emptive effect is outside FDA’s area of expertise. The defendants countered by pointing out that the Supreme Court has in the past accorded considerable deference to FDA’s views on pre-emption of state law. In particular, in Medtronic, Inc v Lohr, 518 US 470, 496 (1996), the court found the FDA to be “uniquely qualified to determine whether a particular form of state law stands as an obstacle to the accomplishment and execution of the full purposes and objectives of Congress, and, therefore, whether it should be pre-empted”.

Colacicco next argued that no deference is due FDA’s position on preemption because its position has not been consistent. Colacicco maintained that in its 2000 rule proposal, the FDA stated that the proposed rule did not pre-empt state law. However, as pointed out by the FDA in its amicus brief, this contention ignores the fact that the agency has consistently expressed similar views on pre-emption in numerous amicus briefs since 2000. In order to warrant deference, the agency must put forward a permissible interpretation of its regulations. In this regard, Colacicco argues that deference is inappropriate because: in the labelling regulations there is no ambiguity over the threshold showing necessary before courts are permitted to take an agency’s view into account; and the FDA interpretations are inconsistent with the language of the regulations. More specifically, Colacicco argues that the plain language of FDA regulations allows a drug manufacturer to unilaterally add or strengthen warnings by filing what is known as a ‘changes being effected’ (CBE) application once there is reasonable evidence of an association of a risk with a drug (see 21 CFR section 314.70). As such, he argued that FDA requirements reflect only minimum standards for prescription drug labelling; state law therefore complements, rather than conflicts with, the FDA’s labelling regulations.

In response, the defendants maintained that FDA regulations do not permit drug manufacturers to unilaterally add or strengthen warnings without approval. Although manufacturers have the option of adding or strengthening warnings, all such labelling changes must be approved by the FDA. The defendants and FDA further noted that, should the FDA disapprove a CBE change, a drug that is already in the marketplace will be deemed misbranded and the manufacturer will be subject to enforcement action.

FDA’s amicus brief adds support to the defendant’s argument. FDA argues that if it has determined that a particular warning is inappropriate, it would frustrate the regulatory scheme if manufacturers could be held liable under state law for failing to include the FDA-rejected warning. A contrary decision would permit a judge or jury to second-guess the agency’s determination and interfere with FDA’s authority over drug labelling.

Colacicco Amici

The Colacicco appeal has drawn considerable interest from a variety of individuals and organisations that have filed amicus briefs both in support of and in opposition to pre-emption. In addition to bolstering or opposing the arguments made by the parties, these amicus briefs shed light on the implications of pre-emption in the pharmaceutical product liability context.

The ‘pro’ pre-emption briefs argue that FDA (which is staffed by doctors and scientists) is uniquely qualified to judge the adequacy of drug labelling and that secondguessing of FDA determinations regarding the adequacy of warnings by lay jurors will undermine the FDA’s objective to ensure the safety and effectiveness of drugs. Faced with potential liability for inadequate warnings, manufacturers may inundate the FDA with requests for scientifically unjustified warnings in an effort to foreclose state-law liability. The amici further argue that if courts determine that FDA labelling requirements merely impose minimum standards, the tendency for manufacturers to over-warn is inevitable. Over-warning poses a significant threat to patient safety and public health because consumers may be discouraged from using a beneficial drug and valid warnings may lose their signifi- cance or appear less credible. Finally, according to the amici, pharmaceutical companies could face liability for warnings they were powerless to change. By way of example, amici point to the Colacicco case, where the FDA had determined that the warnings the plaintiff claimed should have been added to the labelling (under state law) would render the drug misbranded under the FDCA.

A number of groups have filed amicus briefs opposing pre-emption. They assert that the FDA lacks the capability to adequately ensure prescription drug safety. In this regard, the amici point to recent events relating to Vioxx as evidence of FDA shortcomings. They argue that the FDA is limited in its ability to evaluate drug risks because of under-reporting of adverse events. They further maintain that instead of independently deciding what labelling is appropriate, the FDA often negotiates and eventually allows the manufacturer to dictate what warnings will be included. In essence, the amici argue that FDA protection is not enough and that state tort law and the potential for liability serves as a check on FDA and encourages the pharmaceutical industry to act independently in the interest of drug safety.

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The outcome of the Colacicco appeal could be a turning point for the pharmaceutical industry, not only in the courtroom but also in how manufacturers interact with FDA and approach prescription-drug labelling. As the first circuit court to address pre-emption in the wake of the preamble, the third circuit’s decision has the potential to solidify the trend in favour of pre-emption and substantially change the profile of pharmaceutical product liability litigation in the United States. Ultimately, the issue will likely have to be decided by the United States Supreme Court.

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