In re Fosamax (Alendronate Sodium) Prods. Liab. Litig.

593 F.Supp.3d 96

IN RE FOSAMAX (ALENDRONATE SODIUM) PRODUCTS LIABILITY LITIGATION

This Opinion Relates to: All Actions

MDL No. 2243

Civil Action No. 3:08-08 (FLW)

United States District Court, D. New Jersey.

Signed March 23, 2022

OPINION

WOLFSON, Chief Judge:

In this failure-to-warn case, more than 500 individuals ("Plaintiffs") who took Fosamax, a drug manufactured by Defendant Merck Sharp & Dohme ("Defendant" or "Merck") to prevent and treat osteoporosis in postmenopausal women, brought suit claiming that they suffered atypical femoral fractures between 1999 and 2010. More than eight years ago, following a bellwether trial, the late Hon. Joel A. Pisano, U.S.D.J., granted summary judgment in favor of Merck, ruling that federal law preempted Plaintiff's state law failure-to-warn claims.¹ In re Fosamax (Alendronate Sodium) Prod. Liab. Litig. , 951 F. Supp. 2d 695, 701, 703-04 (D.N.J. 2013) [hereinafter Glynn ]. On appeal, the Third Circuit vacated and remanded this matter, concluding that preemption presented "a question of fact for the jury," not a question of law for the judge. In re Fosamax (Alendronate Sodium) Prod. Liab. Litig. , 852 F. 3d 268, 271, 293 (3d Cir. 2017) [hereinafter Fosamax ], vacated and remanded , ––– U.S. ––––, 139 S.Ct. 1668, 203 L.Ed.2d 822 (2019). And, in answering that question, the Third Circuit held that the jury must apply a heightened standard of proof, sustaining the preemption defense only if Merck proved it by "clear and convincing evidence." Id. at 285-86. Merck, however, petitioned for a writ of certiorari, which was granted by the United States Supreme Court. In Merck Sharp & Dohme Corp. v. Albrecht , ––– U.S. ––––, 139 S.Ct. 1668, 1676, 1679-80, 203 L.Ed.2d 822 (2019), the Supreme Court vacated and remanded the Third Circuit's decision, holding that the preemption inquiry is "a legal one for the judge, not a jury." Upon remand, the Third Circuit returned the case to this Court to decide "in the first instance whether the plaintiffs’ state law claims are preempted by federal law under the standards described by the Supreme Court." Order at 1, No. 14-1900 (3d Cir. Nov. 25, 2019). The Third Circuit further instructed this Court "to determine the effect of the [Food and Drug Administration's ("FDA" or "Agency")] Complete Response Letter [("CRL")] and other communications with Merck on the issue of whether such agency actions are sufficient to give rise to preemption." Id.

On remand, Merck reiterates its position that federal law preempts Plaintiffs’ state law failure-to-warn claims. In particular, Defendant relies on the FDA's 2019 communication, in the form of a CRL, rejecting a warning concerning atypical femoral fractures that Merck proposed. Plaintiffs, on the other hand, argue that the CRL is not "clear evidence" that the FDA would have rejected any and all warnings. Having reviewed the submission of the parties, the Court finds that based on clear and convincing evidence, Defendant fully informed the FDA of the justifications for its proposed warning, which was adequate under state law and encompassed the injury Plaintiffs allege here, and the FDA, in turn, informed Defendant that it would not approve changing the Fosamax label to include that warning in the CRL. Because the FDA's rejection was predicated on insufficient evidence of a causal link between Fosamax and atypical femoral fractures, it is clear that the Agency would not have approved a differently worded warning about such a risk. Plaintiffs’ state law failure-to-warn claims are therefore preempted, and Defendant's Motion for Summary Judgment is GRANTED .

FACUAL BACKGROUND AND PROCEDURAL HISTORY

The factual background and procedural history of this case, which are largely not in dispute, are primarily adopted from the Supreme Court and Third Circuit's decisions in this matter, as well as Judge Pisano's dual decisions in Glynn and In re Fosamax (Alendronate Sodium) Prod. Liab. Litig. , 2014 WL 1266994, at *17 (D.N.J. Mar. 22, 2014) [hereinafter OTSC Opinion ].

A. Fosamax

Merck manufactures Fosamax, a drug that treats and prevents osteoporosis in postmenopausal women. Merck , 139 S.Ct. at 1668. Fosamax belongs to a class of drugs called "bisphosphonates," which operate on the "remodeling process," where the body breaks down bones and builds them back up. In postmenopausal women, this process can "fall out of sync," id. at 1673, such that the body removes old bone cells faster than it replaces them. When resorption exceeds formation, the result is osteoporosis, or low bone mass that increases the risk of fractures. Fosamax "slows the breakdown of old bone cells and thereby helps postmenopausal women avoid [such] fractures." Id. However, by reducing resorption, the drug may cause some microscopic stress fractures to develop into a specific type of stress fracture known as atypical femoral fractures, or complete breaks that "cause great pain and require surgical intervention to repair." Id. at 1674.

A low energy, or also known as atypical, fracture is defined as one that is caused by the equivalent of a fall from standing height or less, which involves minimal force. A stress fracture is defined as a partial or complete fracture occurring with either normal or increased activity, but without an identifiable external traumatic event. Stress fractures, in this context, are included in the larger group of low-energy fractures. In postmenopausal osteoporotic women, the proximal femur is one of the most commonly affected sites for fractures, as are the pelvis, distal tibia and metatarsals. See Def. Br., Ex. 1 at A2751-52.

B. The Regulatory Framework for Drug Labeling

Congress has charged the FDA with ensuring that every prescription drug on the market is "safe for use under the conditions prescribed, recommended, or suggested" in its "labeling." 21 U.S.C. § 355(d). As that directive suggests, labeling is the "centerpiece" of the FDA's risk management strategy for approved drugs, and the primary means by which the FDA communicates its conclusions about drug safety to the public. 71 Fed. Reg. 3922, 3944. Prospective drug manufacturers, such as Merck, must work with the FDA to develop an appropriate label when they submit a new drug for approval. 21 U.S.C. §§ 355(a), (b), (d)(7) ; 21 C.F.R. § 314.125(b)(6). The FDA closely regulates the safety information on drug labels, down to the exact text of warnings.² 21 U.S.C. § 355(b)(1)(F) ; 21 C.F.R. § 201.57(a).

Drug labels include two sections relevant to this case: a "Precautions" section and an "Adverse Reactions" section. The Precautions section narrowly describes "clinically significant adverse reactions," including any that are "serious even if infrequent." 21 C.F.R. § 201.57(c)(6)(i). The Adverse Reactions section more broadly describes "the overall ... profile of the drug based on the entire safety database," including a list of all "undesirable effect[s], reasonably associated with use." Id. § 201.57(c)(7).

The threshold for placing a warning regarding an adverse event in the Precautions section is "reasonable evidence of a causal association." 21 C.F.R. § 201.57(c)(6)(iii) (providing that the Precautions section "must be revised to include a warning about a clinically significant hazard as soon as there is [such evidence] ... a causal relationship need not have been definitely established"); Fed. Reg. 49,603, 49,604. The FDA designed this standard so as not to dilute "more important warnings" or "deter appropriate use." 73 Fed. Reg. at 49,605, 40,606. In other words, the Precautions section is reserved for a "discrete set" of serious risks that would affect a doctor's prescribing decisions or be "potentially fatal." 71 Fed. Reg. 3922-01, 3946 ; FDA, Guidance for Industry: Warnings and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Human Prescription Drug and Biological Products – Content and Format, at 3 (Oct. 2011). On the other hand, the threshold for warning of an adverse event in the Adverse Reactions section is comparatively lower: "some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event." 21 C.F.R. § 201.57(c)(7).

New information about a drug may require changing its label. 21 U.S.C. §§ 314.80(c), 314.81(b)(2)(i). A drug manufacturer may change its label in one of two ways. More commonly, it may seek advance permission from the FDA through a Prior Approval Supplement Application ("PAS"). 21 C.F.R. § 314.70(b). Alternatively, it may change a label immediately and unilaterally through a Changes Being Effected Application ("CBE") to reflect "newly acquired information" about "evidence of a casual association between the drug and a risk of harm." Merck , 139 S.Ct. at 1673 (quotations omitted); 21 U.S.C. § 314.70(c)(6)(iii)(A); 21 C.F.R. § 314.3(b) (defining "[n]ewly acquired information" to mean, inter alia , risks not previously known or previously underestimated). Whatever method a manufacturer chooses, it must meet the causal thresholds described above, and significantly, the FDA retains authority to reject even a CBE amendment if there is insufficient evidence of a link between the drug and the adverse event. 73 Fed. Reg. 2848, 2851 ; 21 C.F.R. § 314.70(c)(6)(iii)(A) (providing that the FDA will approve a label change only if "the evidence of a causal association satisfies the standard for inclusion in the labeling"); id. §§ 314.125(b)(6), (b)(8).

Because of the availability of the CBE process, "a drug manufacturer will not ordinarily be able to show that there is an actual conflict between state and federal law such that it was impossible to comply with both." Merck , 139 S.Ct. at 1679. At the same time, the FDA will not approve a warning simply out of an abundance of caution whenever a manufacturer posits an association between a drug and an adverse event. As the FDA has long recognized, "[e]xaggeration of risk, or inclusion of speculative or hypothetical risks, could discourage...