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Were state and federal courts to defer sufficiently to FDA determinations of drug safety, the negative consequences of the current liability regime would be much less pronounced. Yet this has often not been the case. In recent years, FDA’s legal authority and scientific expertise over drug labeling and advertising have been implicitly, although repeatedly, questioned in state and federal courts. In response, FDA has intervened in select cases where its authority and expertise may be undermined by state law. In the two cases discussed below, state law claims against drug manufacturers concerning the adequacy of labeling and advertising were allowed to proceed, even though the requested relief, if awarded, would squarely conflict with specific prior determinations made by FDA. In each of these cases, an FDA Shield Law on the Michigan model might well have made FDA involvement unnecessary.

More recently, in the preamble to its long-awaited Physician Labeling Rule, FDA explicitly set forth its view that FDA approval of prescription drug labeling preempts most state-law tort claims based on alleged deficiencies in FDA-approved labeling. Nonetheless, it is unclear whether courts hearing state tort cases will give this language an appropriate degree of deference. At least until an authoritative ruling requires all courts in the United States to recognize the validity of FDA’s exercise of preemptive authority over drug labeling, state-bystate legal reform will remain an important aspect of efforts to ensure a pharmaceutical-liability regime that serves the long-term health interests of all Americans.

Dowhal v. Smithkline Beecham Consumer Healthcare

            In 1999, Paul Dowhal filed a citizen suit in the Superior Court of the State of California, San Francisco County, under the state’s Safe Drinking Water and Toxic Enforcement Act (Proposition 65), against manufacturers, distributors, and retailers of over-the-counter nicotine replacement products.1 California environmental protection authorities had listed nicotine as a developmental and reproductive toxicant.2 Dowhal argued that the defendants were required to disseminate publicly—through labeling— a statement that the State of California had determined that these products cause birth defects or other reproductive harm.3

Specifically, Dowhal sought to require the defendants to label over-the-counter nicotine replacement products with the following statement: “Warning: This product contains a chemical known to the State of California to cause birth defects or other reproductive harm.” Alternatively, the plaintiff sought an injunction requiring the following warning or a comparable one: “If pregnant or breast-feeding, ask a health professional before use. Nicotine, whether from smoking or medication, can harm your baby. First try to stop smoking without the patch.”

A year after filing his complaint under Proposition 65, Dowhal submitted a citizen petition to FDA. That petition asked FDA to require manufacturers of nicotine replacement products to label their products with a warning like the “harm your baby” warning set forth above. After reviewing the pertinent scientific evidence, FDA rejected the proposal, including the information submitted with the petition. FDA determined that the requested warning was not scientifically supportable. FDA concluded, further, that the Proposition 65 warning could cause pregnant and nursing women to conclude, mistakenly, that using a nicotine replacement therapy product presents health risks that are as grave as those associated with smoking.

Indeed, FDA had prohibited manufacturers from labeling their products voluntarily with a Proposition 65 warning. In January 1997, FDA denied a request from one manufacturer of nicotine replacement products for permission to change the label for its product to add Proposition 65 warning language. The agency advised the manufacturer to use the FDAapproved labeling, which includes a statement encouraging pregnant and nursing women to seek professional advice before using nicotine replacement therapy. In March 2001, FDA confirmed in a letter to other manufacturers that using additional warning language to satisfy Proposition 65 could render their products misbranded under the Federal Food, Drug, and Cosmetic Act (FDCA).4

The Superior Court granted summary judgment to the defendants on the ground that Proposition 65 is impliedly preempted by the FDCA. Dowhal appealed to the California Court of Appeal. FDA submitted an amicus curiae brief supporting the defendants.5 The agency’s legal theory rested on the doctrine of conflict preemption: First, the labeling sought by Dowhal was preempted by the FDCA because it would be impossible for the defendants to comply with both Proposition 65 (as interpreted by the plaintiff) and with the FDCA (as applied by FDA). In essence, if the defendants were to adopt the warning language advocated by Dowhal, they would be in violation of the prohibition in the FDCA against selling misbranded drugs.6 Second, application of Proposition 65 to nicotine replacement products in the manner advocated by Dowhal would pose an obstacle to the accomplishment of the full purposes and objectives of the FDCA.

The Court of Appeal reversed the Superior Court’s decision in July 2002, finding that in the FDA Modernization Act (FDAMA), Congress intended to exempt Proposition 65 from preemption, and that this disposed of the defendants’ preemption arguments.7 The court refused to resolve whether, by complying with the FDCA and not including the warning language advocated by Dowhal, the defendants exposed themselves to Proposition 65 liability.8

In August 2002, the defendants petitioned the Supreme Court of California for review of the Court of Appeal’s decision. FDA submitted a letter brief in support of the petition the following month.9 In October 2002, the Supreme Court of California granted the petition.10 In August 2004, that court reversed the decision of the Court of Appeal. Concluding that FDA had barred all possible warnings that would have complied with Proposition 65,11 the Supreme Court of California applied the doctrine of conflict preemption to hold that Proposition 65 was preempted insofar as it conflicted with FDA requirements.12

In so deciding, the court explicitly clarified that it was immaterial to the question of preemption whether Dowhal’s warning could in some sense be classified as truthful.13 As the Supreme Court of California correctly explained, FDA’s authority is not limited to prohibiting statements that are false.14 The agency is also charged with prohibiting those statements which, though perhaps formally “true,” would be misleading.15 The Supreme Court of California found that FDA was well within its authority to conclude that the labeling of a nicotine replacement product must indicate that it is better for a pregnant woman to use a nicotine replacement product than to continue smoking.16

Motus v. Pfizer, Inc.

            When FDA specifically considers and rejects language regarding the risk of a particular adverse event allegedly associated with a prescription drug or class of drugs, courts applying state tort law should not allow failure-to-warn claims based on the absence of such language. Yet that is exactly what happened in a lawsuit filed in California against Pfizer Inc. The case involves ZOLOFT (sertraline HCl), a drug in the selective serotonin reuptake inhibitor (SSRI) class used to treat depression.

Pfizer submitted its original new drug application (NDA) for ZOLOFT in 1988. FDA evaluated all relevant scientific data and found no causal link between the drug and an increased risk of suicide. In 1990, FDA convened a meeting of the Psychopharmacological Drugs Advisory Committee (PDAC) to assess ZOLOFT.17 The committee unanimously concluded that the drug was safe when used to treat depression.18 The original labeling approved with the NDA for ZOLOFT on December 30, 1991, included precautionary language concerning the risk of suicide in depressed patients, but did not specifically warn that the drug increased suicidal ideation or the risk of suicide.19 ZOLOFT later was approved for use in four other psychiatric disorders.

On three other occasions, FDA specifically considered and rejected claims that another SSRI causes suicide. In 1990 and 1991, FDA received two citizen petitions alleging a link between the SSRI PROZAC (fluoxetene) and suicide. One petition sought market withdrawal; the other asked FDA to require a “black box warning” in PROZAC’s labeling concerning a putative link between the drug and suicide. FDA examined the data concerning the risk of suicide and other violent behavior and SSRIs, and rejected both petitions. In 1997, FDA declined to grant a third citizen petition requesting additional suicide warning language in the labeling for PROZAC.

FDA also obtained expert advice as to whether antidepressants generally increase patients’ suicide risk. In 1991, FDA requested that the PDAC review the scientific evidence relating to the risk of suicide and the pharmacological treatment of depression. On September 20, 1991, the PDAC determined unanimously that the evidence did not indicate that use of any particular drug or class of drugs to treat depression heightens the risk of suicide. The advisory committee also heard remarks from the then-Director of FDA’s Division of Neuropharmacological Drug Products concerning the risk that modifying the labeling could misleadingly overstate the risk of suicide and cause a reduction in the use of pharmacotherapy to treat depression.

In 2002, FDA conducted yet another internal review of scientific evidence regarding SSRIs and suicide.20 The review revealed no difference in the risk of suicide between patients using SSRIs and patients on placebo.21 However, after reviewing further studies the agency refined its position in late 2004 and early 2005.22 FDA now warns that antidepressants, including Zoloft, “may increase suicidal thoughts and actions in about 1 out of 50 people 18 years or younger,” and that “[s]everal recent publications report the possibility of an increased risk for suicidal behavior in adults who are treated with antidepressant medications.”23

Despite FDA’s position prior to October 2002, Pfizer has been a target of state law failure-to-warn claims based on the absence of additional warning language concerning suicide in the labeling for ZOLOFT. Notably, in November 1998, a candidate for the city council and failing businessman named Victor Motus visited his doctor, appearing depressed and frustrated.24 His physician diagnosed moderate depression and prescribed ZOLOFT 25 mg for seven days, followed by 50 milligrams of ZOLOFT for fourteen days.25 Six days after visiting his doctor, Motus committed suicide by shooting himself.26 His wife sued Pfizer, claiming that, under California law, the company had acted negligently by failing to warn adequately in the package insert and marketing materials that ZOLOFT could cause suicide.27

The United States District Court for the Central District of California (to which the case had been removed on the ground of diversity) held that federal law did not preempt the plaintiff’s state tort law claims.28 In making this finding, the court relied on cases finding that FDA’s regulation of labeling did not preempt all tort actions.29 The court did not carefully analyze whether requiring the additional warning language sought by the plaintiff would conflict with FDA’s conclusion that SSRIs do not heighten the risk of suicide.

FDA filed an amicus curiae brief in the United States Court of Appeals for the Ninth Circuit, contending that the plaintiff’s state law claims could not stand.30 The FDA-approved labeling for ZOLOFT discusses the risk of suicide that accompanies depression, but does not identify ZOLOFT as a potential cause of suicide. The labeling thus reflects FDA’s specific finding that ZOLOFT does not cause suicide, contrary to the language that would be included in the labeling were the plaintiff to prevail.

In affirming the judgment of the district court, the Ninth Circuit explicitly declined to reach the district court’s preemption holding.31 Instead, the Ninth Circuit rested its conclusion on the prescribing doctor’s failure to read Pfizer’s warnings or rely on information provided by Pfizer’s representatives in making his decision to prescribe ZOLOFT.32 As the doctor would not have been aware of any warning Pfizer issued, Mrs. Motus could not prevail on a claim that the inadequacy of Pfizer’s warnings caused her husband’s death.”

 

*Daniel Troy is a partner in Sidley Austin’s Life Sciences Practice as well as Appellate Litigation group. The article from which this piece is excerpted can be obtained at www.fed-soc.org.

 

Endnotes

 

1 Dowhal v. SmithKline Beecham Consumer Healthcare, A094460, 2002 Cal. App. LEXIS 4384, at ***2 n.1 (Cal. Ct. App. July 12, 2002) (reversing trial court decision granting summary judgment for defendants on preemption grounds), review granted, 56 P.3d 1027 (Cal. 2002) (en banc), judgment reversed, 88 P.3d 1 (Cal. 2004).

2 2002 Cal. App. LEXIS 4384, at ***3 (citing CAL. CODE REGS. tit. § 12000(c)).

3 Id. at ***5.

4 Id. at ***9.

5 Amicus Curiae Brief of the United States of America in Support of Defendants/Respondents SmithKline Beecham Consumer Healthcare LP, et al., Dowhal v. SmithKline Beecham, Case No. A094460 (Cal. Ct. App. filed Mar. 22, 2002)

6 Id. at 13.

7 2002 Cal. App. LEXIS 4384, at ***16-17 (citing 21 U.S.C. § 379r).

8 Id. at ***29-30.

9 Letter from Robert D. McCallum, Jr., Ass’t Attorney General, et al., to Frederick K. Ohlrich, Supreme Court Clerk/Administrator, Dowhal v. SmithKline Beecham Consumer Healthcare LP, et al. (S. Ct. No. S-109306) (filed Sept. 12, 2002).

10 Dowhal, 56 P.3d 1027 (Cal. 2002).

11 Dowhal v. SmithKline Beecham Consumer Healthcare, 88 P.3d 1, 11-12 (Cal. 2004).

12 Id. at 11.

13 Id. at 12.

14 Id. 15 Id.

16 Id. at 14-15.

17 Motus v. Pfizer, Inc., 127 F. Supp. 2d 1085, 1088 (C.D. Cal. 2000) [hereinafter Motus I], summary judgment granted, Motus v. Pfizer, Inc., 196 F. Supp. 2d 984, 986 (C.D. Cal. 2001) [hereinafter Motus II], appeal docketed, Motus v. Pfizer, Inc., Case Nos. 02-55372 & 02-55498 (9th Cir. Mar. 12, 2002).

18 Motus I, 127 F. Supp. 2d at 1088. The facts of FDA’s review of the NDA for ZOLOFT, and its consideration of the need for suicide warnings in the labeling of SSRIs as a class, are recounted id. at 1089-90.

19 The “Precautions” section of the proposed labeling, which FDA instructed Pfizer to use “verbatim,” included the following statement:

Suicide—The possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high risk patients should accompany initial drug therapy. Prescriptions for Zoloft (sertraline) should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.

Id. at 1088.

20 Amicus Brief for the United States in Support of the DefendantAppellee and Cross-Appellant, and in Favor of Reversal of the District Court’s Order Denying Partial Summary Judgment to Defendant-Appellee and Cross-Appellant, Motus v. Pfizer, Inc., Case Nos. 02-55372 & 02-55498, at 22 (9th Cir. filed Sept. 3, 2002) (citation omitted).

21 Id.

22 Amicus Brief for the United States, Kallas v. Pfizer, Inc., No. 2:04-cv-998 (D. Utah filed Sept. 15, 2005).

23 FDA Alert: Suicidal Thoughts or Actions in Children and Adults, July 2005, http://www.fda.gov/cder/drug/infopage/sertraline/ default.htm.

24 Motus II, 196 F. Supp. 2d at 986.

25 Id.

26 Id. at 987.

27 Id. at 984.

28 Motus I, 127 F. Supp. 2d at 1087.

29 Id. at 1092.

30 Amicus Brief, supra note 100.

31 Motus v. Pfizer, Inc., 358 F.3d 659, 660 (9th Cir. 2004).

32 Id. at 660.

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