Weiss v. Fujisawa Pharmaceutical Co.

Citations: 464 F. Supp. 2d 666; 2006 U.S. Dist. LEXIS 86179; 2006 WL 3422688Docket: Civil Action 5:05-527-JMH

Court: District Court, E.D. Kentucky; November 28, 2006; Federal District Court

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Philip C. Weiss and other plaintiffs filed a lawsuit against Fujisawa Pharmaceutical Co. and Novartis Pharmaceutical Corporation (NPC) alleging failure-to-warn claims related to the use of the drugs Elidel and Protopic for treating atopic dermatitis. Weiss claims to have developed cancer and other serious health issues as a result of these medications, asserting that NPC was aware of significant health risks associated with Elidel since at least 1999 but failed to inform him or his physician. 

NPC moved to dismiss these claims, arguing they are preempted by the Food, Drug, and Cosmetic Act (FDCA) and FDA regulations. The court determined that the plaintiffs' failure-to-warn claims were not preempted, as the drugs in question were approved prior to the 2006 revisions of FDA labeling regulations. Under the FDCA, the FDA must approve drugs as safe and effective, and manufacturers are required to update product labeling based on new safety information. While manufacturers typically need FDA approval for changes to labeling, they can independently strengthen warnings if there is reasonable evidence of serious hazards without prior FDA consent. Thus, the court found that state law claims could proceed.

The FDCA defines a drug as misbranded if its labeling is false or misleading (21 U.S.C. 352(a)). However, manufacturers are not restricted from communicating information about potential dangers through other means, such as warnings to health care professionals regarding harmful adverse effects. Additional warnings, contraindications, adverse reactions, and precautions can be included in labeling and advertising, and information can be disseminated via letters to healthcare providers (e.g., 'Dear Doctor' letters), as these communications are sometimes expected by FDA regulations (44 Fed.Reg. 37434, 37447; 21 C.F.R. 200.5). The FDA approved NPC's application to market Elidel for atopic dermatitis on December 13, 2001, with labeling indicating no increased cancer rates in humans but noting increased lymphoma in high-dose animal studies. Consequently, ongoing studies to monitor malignancy incidence related to Elidel's long-term use were required. In October 2003, discussions at a Pediatric Advisory Subcommittee meeting acknowledged potential lymphoma associations with systemic exposure to calcineurin inhibitors, noting challenges in assessing cancer risks due to long latency periods and low incidence rates. Although there were suggestions for risk management strategies, no formal recommendations on labeling were made. A subsequent Pediatric Advisory Committee meeting on February 15, 2005, focused on potential cancer risks in children, particularly concerning off-label use in infants, with prior studies suggesting chronic exposure might increase lymphoma and skin cancer risks.

FDA conducted new animal studies and received additional reports indicating a potential association between calcineurin inhibitors, such as Elidel and Protopic, and an increased cancer risk, particularly in young children. The Office of Pediatric Therapies and the Division of Pediatric Drug Development recommended modifying the labels of these drugs to indicate this potential cancer risk. During a February 15 meeting, the Pediatric Advisory Committee voted to suggest a boxed warning due to the potential increased risk of lymphoma and malignancies, while acknowledging the lack of sufficient human data to determine the cancer risk from topical use of these inhibitors. On March 10, 2005, FDA issued a public health advisory regarding this risk, and on January 19, 2006, it approved revised labeling for Elidel, which included a boxed warning about rare malignancies reported in patients using topical calcineurin inhibitors and advised against long-term use.

FDA maintains that its approval of drug labeling preempts conflicting state laws, a position it has held since around 2001, despite earlier statements indicating it did not intend to influence civil tort liability or preclude states from imposing additional requirements. In recent regulatory developments, FDA asserted that state law actions could threaten its role as the federal agency responsible for drug evaluation and regulation. In an ongoing products liability lawsuit regarding Elidel, FDA confirmed that state tort law is preempted if it imposes liability based on warnings that FDA has either rejected or deemed unnecessary for the safe use of a drug.

The FDA cannot determine if the plaintiffs' failure-to-warn claim regarding Elidel is entirely preempted due to a lack of specificity in the plaintiffs' assertions. However, the FDA has indicated that certain failure-to-warn claims may be preempted by federal law. Specifically, claims suggesting that Elidel causes lymphoma are preempted under federal conflict preemption since they contradict the FDA's 2006 conclusion that causation is unestablished. Additionally, claims regarding risks not listed on Elidel's approved label would also be preempted without supporting scientific evidence. 

The document outlines that NPC argues state law failure-to-warn claims are preempted by FDA regulations based on the conflict preemption doctrine, which applies when compliance with both state and federal laws is impossible or when state law obstructs federal objectives. Courts generally presume that state law is not overridden unless Congress's intent to preempt is clear. In considering a motion to dismiss, the court must view the complaint favorably towards the plaintiff and accept well-pleaded factual allegations as true.

The court discusses three types of deference it may apply to the FDA's position: Chevron deference for administrative interpretations of statutes, Auer deference for agency interpretations of their own regulations, and Skidmore deference for interpretations that are persuasive but not controlling. Due to inconsistencies in the FDA's position, the court concludes that only limited deference is appropriate. Specifically, the FDA's preamble and letter to Judge Dalzell do not qualify for Chevron deference, as they lack the force of law compared to formal regulations and are not subject to notice and comment procedures.

The rule, while having the characteristics of a published regulation, lacks the formal notice and comment rulemaking process, limiting its deference primarily to internal guidelines. Advisory opinions, as defined by 21 C.F.R. 10.85(d)(1), include elements of Federal Register notices outside the proposed or final regulation text. Although the preamble and correspondence with Judge Dalzell do not qualify for Chevron deference, they typically receive Auer deference, meaning the agency's interpretation of its own regulations is authoritative unless clearly erroneous or inconsistent. However, the FDA's inconsistent positions reduce their deference to Skidmore standard, which evaluates the persuasiveness of the agency's reasoning and consistency with prior interpretations. The court aligns with the Eastern District of Pennsylvania's perspective, granting significant weight to FDA's efforts in clarifying ambiguities in the FDCA and its regulations. However, no deference is afforded when the agency attempts to interpret legislative intent that would override the presumption against preemption. Specifically, the FDA's stance against failure-to-warn claims related to pre-approval conduct is supported. The Sixth Circuit's precedents on fraud-on-the-FDA claims suggest such claims are likely preempted, as established in Buckman Co. v. Plaintiffs' Legal Committee, emphasizing that the relationship between the FDA and regulated entities is fundamentally federal, which negates the presumption against preemption.

State-law fraud-on-the-FDA claims are preempted because they conflict with the FDA's regulatory authority. While the Supreme Court's decision in Buckman pertains specifically to fraud-on-the-FDA claims, it does not apply to this case, which involves failure-to-warn claims regarding prescription drugs not covered by the Medical Device Amendments (MDA). However, the Sixth Circuit has extended Buckman's reasoning, declaring that some failure-to-warn claims can also be preempted. The court identified two interpretations of a failure-to-warn claim: one regarding the adequacy of FDA-approved warnings and another suggesting that the manufacturer had new information that warranted additional warnings. Claims based on the adequacy of FDA-approved warnings would also be preempted under the reasoning of fraud-on-the-FDA claims.

The FDA's regulations provide manufacturers with several means to update warnings post-approval, including the ability to enhance warnings without prior FDA approval if they remain non-misleading. Manufacturers may also communicate new evidence to the FDA or healthcare providers. In this case, the FDA had not definitively linked topical calcineurin inhibitors to cancer risk at the time Elidel was prescribed, and it's possible that NPC had information not available to the FDA that could have been shared. Thus, state law failure-to-warn claims would not interfere with the FDA's regulatory framework, which allows for updates to warnings.

Consequently, the court denied NPC's motion to dismiss the failure-to-warn claims on federal preemption grounds, allowing the case to proceed.

New regulations that preempt state failure-to-warn claims, unlike the previous regulations, raise a retroactivity issue. Generally, a change in regulation does not apply retroactively unless explicitly authorized. The FDA claims that both the old and new regulations preempt state law, leading to a question of the level of deference the Court should give to the FDA's interpretation. "Off-label use" refers to prescribing medications for unapproved indications, which, despite being discouraged for manufacturers to promote, is prevalent; for instance, approximately 500,000 prescriptions for Elidel and Protopic were issued for children under two years old, despite these drugs not being approved for that age. The Sixth Circuit addressed the preemption of failure-to-warn claims based on post-approval information in Cupek v. Medtronic, ultimately finding such claims preempted under the Medical Devices Amendment, which contains a specific preemption provision.