In re Fosamax Products Liability Litigation

James M. Beck

Since 2008, parties to pharmaceutical product liability cases have struggled with the “clear evidence” implied preemption standard articulated by the U.S. Supreme Court in Wyeth v. Levine.¹ In cases of allegedly inadequate warnings about FDA approved prescription drugs, Levine rejected the contention that FDA approval did not, by itself, preempt state-law warning-based claims. Preemption could occur, Levine held, if “clear evidence” showed that “the FDA would not have approved” the label that the plaintiff claim state law required, so that simultaneous compliance with state and federal law would be “impossible.”² Following Levine, courts varied in the rigor that they applied the “would not have approved” standard set by the Supreme Court. However, in those situations where FDA had actually rejected the warning being advocated by the plaintiff, they held that the warning claim was preempted.³ Another area of general agreement was that preemption generally, and the question of what FDA “would have” done in particular, was a question of law for courts to determine.⁴

The Third Circuit departed from both of these points of post-Levine consensus in In re Fosamax (Alendronate Sodium) Products Liability Litigation,⁵ and imposed a standard for impossibility preemption that is literally almost impossible to meet. For this result, and because of the likelihood of further review by the Supreme Court, Fosamax makes this year’s list.

Discussion

Fosamax is an FDA approved prescription drug made by defendant Merck Sharp & Dohme Corp. (Merck). It is FDA approved for prevention and treatment of
osteoporosis in postmenopausal women.⁶ Fosamax is one of a class of drugs, called bisphosphonates, whose chemical properties allow them to retard the resorption of calcium in post-menopausal women’s bones, thereby maintaining bone strength and mass. Retarding calcium loss unfortunately has some drawbacks, or so it is alleged, that over the long term, it can lead to “microcracks” that increase the otherwise very low risk of “atypical” femoral fractures (AFF).⁷ That risk is what the Fosamax litigation is about. This risk of AFF from long-term Fosamax use has also been the subject of FDA review, which gives rise to Merck’s preemption defense. The initial labeling for Fosamax, following FDA approval “in the 1990s”⁸ did not mention AFF. In March 2008, Merck submitted a safety update addressing AFF and, based on some recent medical articles, suggested there might be an association between long-term
bisphosphonate use and AFF. FDA saw the information as a “developing safety signal,” and wanted more information.

FDA did not act before Merck filed an NDA supplement, seeking FDA approval to add AFF-related language to the label that did not confirm causation. Substantial dialogue with FDA ensued, with FDA looking toward classwide labeling for all bisphosphonates. Ultimately, in May 2009, FDA formally approved changes to the Adverse Reactions section but rejected the rest of Merck’s NDA supplement. Almost a year later, FDA publicly stated that research had “not shown a clear connection” between bisphosphonates and AFF. FDA demanded more study. By October 2010, causation was “still not clear,” but the association was strong enough for FDA to “consider label revisions.” FDA-ordered label changes in October 2010 conceded causation was still “not clear,” but informed physicians that AFF “have been reported” in long-term bisphosphonate patients, identifying symptoms to watch for and recommending “interrupting treatment” where those symptoms appeared.

In the resultant litigation, Merck contended that FDA’s actions preempted claims that stronger warnings against AFF should have been given earlier. The District Court handling the Fosamax multi-district litigation (MDL) ultimately agreed, entering summary judgment on implied preemption grounds first in a bellwether case,⁹ and ultimately extending its preemption ruling to the rest of the MDL.¹⁰ The ground for finding preemption was that FDA’s actions constituted “clear evidence” under Levine that FDA would have rejected the label changes demanded by plaintiffs at the time that plaintiffs contended they should have been made:

Preemption is warranted because there is clear evidence that the FDA would not have approved a change to the Precautions section of the Fosamax label prior to plaintiff’s fracture. . . . In May 2009, approximately one month after plaintiff’s fracture, the FDA sent Defendant a letter approving the change to the Adverse Reactions section of the label but denying the change to the Precautions section of the label. The FDA’s rejection constitutes clear evidence that the FDA would not have approved a label change to the Precautions section of the label prior to plaintiff’s injury.¹¹

The Third Circuit vacated and remanded. First, the court addressed the “cryptic and open-ended” nature of the “clear evidence” preemption inquiry under Levine.¹² That standard, predicating preemption on “clear evidence that the FDA would not have approved a change” to a drug’s label,¹³ was, according to the Third Circuit “an anomaly in our preemption jurisprudence: the number of cases applying the clear evidence standard continues to grow, yet the clear evidence standard remains undefined.”¹⁴ The Third Circuit addressed this perceived “anomaly” in two ways. First, it equated Levine’s reference to “clear evidence” with an actual heightened standard of proof. Under Fosamax, for preemption to exist “[t]he manufacturer must prove that the FDA would have rejected a warning not simply by a preponderance of the evidence, as in most civil cases, but by ‘clear evidence,’” which the court translated to mean “clear and convincing evidence.”¹⁵ This imposition of a different, more stringent, burden of proof on preemption—that the defendant must prove it is “highly probable” that FDA would have rejected the change¹⁶ —is incompatible with U.S. Supreme Court precedent, which had rejected heightened standards of proof in the implied preemption context, also in a product liability case.¹⁷

Second, the Third Circuit ignored a mountain of precedent, including many of its own prior decisions, which had held preemption to be a question of law for courts to decide.¹⁸ Instead, in another unique post-Levine ruling, Fosamax held that the “counterfactual” preemption question whether FDA would have rejected the plaintiff’s proposed label change is one for the jury—even where, as in Fosamax, the historical facts establishing that FDA did in fact reject that same label changed are undisputed.¹⁹ Thus, a manufacturer can no longer establish the preemption defense pretrial, absent a “‘smoking gun’ rejection letter from the FDA.”²⁰

The Fosamax court’s rationale was: (1) the question involves the likelihood of a future event; (2) the decision maker must weigh conflicting evidence and draw
inferences; and (3) predicting FDA’s actions requires assessment of the motives and thought processes of FDA officials.²¹ Fosamax considered each of these inquires “typically understood to be fact questions committed to the jury rather than the court.”²² That led to the ultimate conclusion in Fosamax that “[a] state-law failure to warn claim will only be preempted if a jury concludes it is highly probable that the FDA would not have approved a label change.”²³ Thus, even though FDA had in fact rejected the same warning that the plaintiffs sought in the subsequent litigation, the Third Circuit reversed because a jury could
speculate about why FDA did what it did:

Once the FDA rejected [defendant’s] proposal, the ball was back in [its] court to submit a revised, corrected proposal. A reasonable juror could therefore conclude that it was [defendant’s] failure to re-submit a revised [warning change] without stress-fracture language, rather than the FDA’s supposedly intransigent stance on the science, that prevented the FDA from approving a label change.²⁴

To affirm summary judgment on preemption, Fosamax requires that a court must find “that no reasonable juror could conclude that it is anything less than highly probable that the FDA would have rejected Plaintiff’s proposed . . . warning had defendant proposed it to the FDA” at a causally relevant time.”²⁵ In the Third Circuit, impossibility preemption under Levine “clear evidence” standard thus became effectively impossible.

Impact

Predictably, plaintiffs in preemption cases across the country immediately latched onto Fosamax and argued that other courts should adopt it. So far, Fosamax has not found wide acceptance.²⁶ Among courts in the Third Circuit, the conflict between Fosamax and prior precedent adds another layer of confusion to preemption cases generally, because the Third Circuit’s rule, when dissonant precedents must be harmonized, is that the “earlier” precedent “is controlling.”²⁷ Thus, whether or not preemption is a question of fact or a question of law, and who is to decide those issues, is now profoundly unsettled in the Third Circuit.

Assuming the Fosamax holding that predicting what FDA would have done on a set of facts that did not, in fact, occur is something to be decided by a jury, what
evidence is going to be available to make those decisions? Unlike almost every other factual question, the issue of what FDA—a federal agency—would have done is not amenable to the usual rules of discovery. Federal agencies, by and large, are immune from civil discovery.²⁸ Thus, the means of proving the “counterfactual” situation postulated in Fosamax are quite limited. Post-Fosamax, issues concerning what FDA might have done with different possible warning proposals are not likely to be decided based on actual evidence, but rather on the basis of each side’s paid FDA expert witnesses, usually former FDA employees, most of whom will not have worked for the agency for many years and thus are not familiar with FDA’s current thinking on any particular issue.

Further, the ability of any “expert” witness, FDA or otherwise, to testify about legal issues, such as how FDA should have interpreted and applied its regulations to a given set of facts, is likewise limited. “Each courtroom comes equipped with a ‘legal expert,’ called a judge, and it is his or her province alone to instruct the jury on the relevant legal standards.”²⁹ Between the restrictions imposed by FDA on factual discovery and the restrictions of the rules of evidence on expert testimony on questions of law, the likelihood that juries will make informed decisions on the issues Fosamax would force them to decide is relatively small.

Fosamax has, not surprisingly, been appealed to the U.S. Supreme Court.30 The petition for certiorari remains pending. In a development suggesting that the
Supreme Court is giving the Fosamax petition serious consideration, on December 4, 2017, the Court invited the Solicitor General to file an amicus curiae brief stating the federal government’s—and thus FDA’s—view on whether the issues raised warrant grant of the petition.31 Should the Supreme Court elect to hear the Fosamax appeal, the eventual decision would certainly rank among the most important drug/medical device preemption decisions of this decade.³¹

James M. Beck, Senior Life Sciences Policy Analyst at Reed Smith LLP, specializes in complex personal injury and product liability litigation. He is also the founder of, and regular contributor to, the award-winning Drug and Device Law Blog.

1. 555 U.S. 555 (2009) (Levine).
2. Id. at 571
3. Cerveny v. Aventis, Inc., 855 F.3d 1091, 1101-03 (10th Cir. 2017); Rheinfrank v. Abbott
   Laboratories, 680 F. Appx. 369, 386 (6th Cir. 2017). Chambers v. Boehringer Ingelheim Pharmaceuticals,
   Inc., 2018 WL 849081, at *4-5 (M.D. Ga. Jan. 2, 2018); Amos v. Biogen Idec, Inc., 249 F. Supp.3d 690,
   699-700 (W.D.N.Y. 2017); Willis v. Abbott Laboratories, 2017 WL 5988215, at *4 (W.D. Ky. Dec. 1,
   2017); Swanson v. Abbott Laboratories, 2017 WL 5903362, at *7-8 (S.D. Ohio Nov. 28, 2017); Christison
   v. Biogen Idec, Inc., 199 F. Supp.3d 1315, 1347-48 (D. Utah 2016); In re Depakote, 87 F. Supp.3d 916,
   921-23 (S.D. Ill. 2015); Cleary v. Biogen Inc., 2017 WL 4126240, at *5-6 (Mass. Super. Sept. 13, 2017);
   Gentile v. Biogen Idec, Inc., 2016 WL 4128159, at *8 (Mass. Super. July 25, 2016); In re Byetta Cases,
   2015 WL 7184655, at *14-15(Cal. Super. Nov. 13, 2015).
4. Guilbeau v. Pfizer, Inc., 880 F.3d 304, 318 (7th Cir. 2018); Cerveny, 855 F.3d at 1096; Caplinger
   v. Medtronic, Inc., 784 F.3d 1335, 1343 (10th Cir. 2015); In re Pharm. Industry Average Wholesale Price
   Litigation, 582 F.3d 156, 173 (1st Cir. 2009); Lofton v. McNeil Consumer & Specialty Pharmaceuticals,
   672 F.3d 372, 375 (5th Cir. 2012); Risperdal & Invega Product Liability Cases, 2017 WL 4100102, at *7
   (Cal. Super. March 16, 2017), reconsideration denied, 2017 WL 4479317, at *2 (Cal. Super. July 24,
   2017).
5. 852 F.3d 268 (3d Cir. 2017).
6. In re Fosamax (Alendronate Sodium) Products Liability Litigation, 852 F.3d 268, 271 (3d Cir.
   2017) (Fosamax).
7. See Donnelly et al., “Atypical Femoral Fractures: Epidemiology, Etiology, & Patient
   Management,” 6(3) Current Opinion in Support of Palliative Care, 348 (Sept. 2012),
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556525/; Fosamax, 852 F.3d at 272.
8. Fosamax, 852 F.3d at 271.
9. In re Fosamax (Alendronate Sodium Products Liability Litigation, 951 F. Supp. 2d 695, 703-04
   (D.N.J. 2013).
10. In re Fosamax (Alendronate Sodium): Products Liability Litigation, 2014 WL 1266994, at *15-17
    (D.N.J. Mar. 26, 2014).
11. Fosamax, 951 F. Supp.2d 02 (citation omitted).
12. 853 F.3d at 282.
13. Levine, 555 U.S. at 571.
14. 853 F.3d at 284.
15. Id. at 285.
16. Id. at 286.
17. “Neither do we believe that the pre-emption provision, the saving provision, or both together,
    create some kind of ‘special burden’ beyond that inherent in ordinary pre-emption principles − which
    ‘special burden’ would specially disfavor pre-emption here.” Geier v. American Honda Motor Co., 529
    U.S. 861, 870 (2000).
18. Two of those prior decisions Fosamax dismissed as “offhand” rulings. 852 F.3d at 288 & n.106
    (disregarding rulings in In re Federal-Mogul Global Inc., 684 F.3d 355, 364 n.16 (3d Cir. 2012), and Horn
    v. Thoratec Corp., 376 F.3d 163, 166 (3d Cir. 2004)). However, many more such rulings exist, all
    unacknowledged by the Fosamax court. See South Jersey Sanitation Co. v. Applied Underwriters Captive
    Risk Assurance Co., 840 F.3d 138, 143 (3d Cir. 2016); Roth v. Norfalco LLC, 651 F.3d 367, 374 (3d Cir.
    2011); Elassaad v. Independence Air, Inc., 613 F.3d 119, 124 (3d Cir. 2010); Deweese v. National
    Railroad Passenger Corp., 590 F.3d 239, 244 n.8 (3d Cir. 2009); Orson, Inc. v. Miramax Film Corp., 189
    F.3d 377, 380 (3d Cir. 1999) (en banc); Taj Mahal Travel, Inc. v. Delta Airlines, Inc., 164 F.3d 186, 190
    (3d Cir. 1998); Travitz v. Northeast Dep’t ILGWU Health & Welfare Fund, 13 F.3d 704, 708 (3d Cir.
    1994); Pennsylvania Medical Society v. Marconis, 942 F.2d 842, 846 (3d Cir. 1991); Ayers v.
19. 852 F.3d at 297.
20. Id. at 294.
21. Id. at 289-91.
22. Id. at 291.
23. Id. at 293
24. Id. at 299.
25. Id. at 296.
26. To date, Fosamax has been rejected or distinguished in the following decisions: Cerveny v.
    Aventis, Inc., 855 F.3d 1091, 1099, 1103 (10th Cir. 2017) (court “reticent” to follow Fosamax; imposing
    “bright line” preemption test instead); In re Smith & Nephew Birmingham Hip Resurfacing (BHR) Hip
    Implant Products Liability Litigation, ___ F. Supp.3d ___, 2018 WL 1471684, at *6 (D. Md. March 26,
27. United States v. Joseph, 730 F.3d 336, 341 (3d Cir. 2013). Accord, e.g., Pardini v. Allegheny
    Intermediate Unit, 524 F.3d 419, 426 (3d Cir. 2008) (Third Circuit “has long held that if its cases conflict,
    the earlier is the controlling authority and the latter is ineffective”).
28. See United States ex rel. Touhy v. Ragen, 340 U.S. 462, 468 (1951) (federal agencies generally
    have the authority to preclude their personnel from being subjected to discovery in third-party litigation);
    Giza v. HHS, 628 F.2d 748, 751-52 (1st Cir. 1980) (FDA properly precluded discovery by valid
    regulation).
29. Burkhart v. Washington Metropolitan Area Transit Authority, 112 F.3d 1207, 1213 (D.C. Cir.
    1997).
30. See Merck Sharp & Dohme Corp. v. Albrecht, No. 17-290 (U.S. filed Aug. 22, 2017).
31. Id., docket entry, https://www.supremecourt.gov/search.aspx?filename=/docket/docketfiles/html/
    public/17-290.html. The government’s brief has not yet been filed.