In re Fosamax (Alendronate Sodium) Prods. Liab. Litig., s. 14-1900 et al.*

• Decision Date: 22 March 2017
• Docket Number: Nos. 14-1900 et al.*,s. 14-1900 et al.*
• Citation: 852 F.3d 268
• Parties: IN RE: FOSAMAX (ALENDRONATE SODIUM) PRODUCTS LIABILITY LITIGATION
• Court: U.S. Court of Appeals — Third Circuit

852 F.3d 268

IN RE: FOSAMAX (ALENDRONATE SODIUM) PRODUCTS LIABILITY LITIGATION

Nos. 14-1900 et al.*

United States Court of Appeals, Third Circuit.

Argued June 30, 2016
Opinion Filed: March 22, 2017

David C. Frederick, Esq. [Argued], Kellogg Hansen Todd Figel & Frederick, 1615 M Street NW, Suite 400, Washington, DC 20036, Edward Braniff, Esq., Michael E. Pederson, Esq., Weitz & Luxenberg, 700 Broadway, New York, NY 10003, Donald A. Ecklund, Esq., Carella Byrne Cecchi Olstein Brody & Agnello, 5 Becker Farm Road, Roseland, NJ 07068, Counsel for Appellant

John H. Beisner, Esq. [Argued], Jessica D. Miller, Esq., Geoffrey M. Wyatt, Esq., Skadden Arps Slate Meagher & Flom, 1440 New York Avenue N.W., Washington, D.C. 20005, Andrew T. Bayman, Esq., Chilton D. Varner, Esq., King & Spalding, 1180 Peachtree Street, N.E., Atlanta, GA 30309, Karen A. Confoy, Esq., Fox Rothschild, 997 Lenox Drive, Princeton Pike Corporate Center, Building 3, Lawrenceville,

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NJ 08648, Wilfred P. Coronato, Esq., Hughes Hubbard & Reed, 101 Hudson Street, Suite 3601, Jersey City, NJ 07302, David J. Heubeck, Esq., Stephen E. Marshall, Esq., Paul F. Strain, Esq., Venable, 750 East Pratt Street, Suite 900, Baltimore, MD 21202, Counsel for Appellee

Todd N. Hutchison, Esq., Alfred W. Putnam, Jr., Esq., Carol F. Trevey, Esq., Drinker Biddle & Reath, 18^th& Cherry Streets, One Logan Square, Suite 2000, Philadelphia, PA 19103, Counsel for Amicus Curiae Pharmaceutical Research and Manufacturers of America

Before: FUENTES, CHAGARES, and RESTREPO, Circuit Judges

OPINION OF THE COURT

FUENTES, Circuit Judge.

Beginning in 2010, hundreds of plaintiffs filed personal-injury suits against the drug manufacturer Merck Sharp & Dohme, alleging that the osteoporosis drug Fosamax caused them to suffer serious thigh bone fractures. Each Plaintiff brought a state-law tort claim alleging that Merck failed to add an adequate warning of the risk of thigh fractures to Fosamax's FDA-approved drug label. Many Plaintiffs also brought a variety of additional claims including defective design, negligence, and breach of warranty.

Plaintiffs' suits were consolidated for pretrial administration in a multi-district litigation in the District of New Jersey. Following discovery and a bellwether trial, the District Court granted Merck's motion for summary judgment and dismissed all of Plaintiffs' claims on the ground that they were preempted by federal law. The District Court based its ruling on the Supreme Court's decision in Wyeth v. Levine ,¹ which holds that state-law failure-to-warn claims are preempted when there is "clear evidence" that the FDA would not have approved the warning that a plaintiff claims was necessary.

We will vacate and remand. Preemption is an affirmative defense, and Merck has not carried its burden to prove that it is entitled to that defense as a matter of law. The Wyeth "clear evidence" standard is demanding and fact-sensitive. It requires the factfinder to predict a highly probable outcome in a counterfactual world and, therefore, requires a court sitting in summary judgment to anticipate both the range of conclusions that a reasonable juror might reach and the certainty with which the juror would reach them. Here, Plaintiffs have produced sufficient evidence for a reasonable jury to conclude that the FDA would have approved a properly-worded warning about the risk of thigh fractures—or at the very least, to conclude that the odds of FDA rejection were less than highly probable. Under Wyeth and Rule 56, that is enough for Plaintiffs to defeat summary judgment and proceed to trial.

I. BACKGROUND

A. Fosamax and Atypical Femoral Fractures

Fosamax is a drug manufactured by Merck that belongs to a class of drugs known as bisphosphonates. The Food and Drug Administration ("FDA") approved Fosamax in the 1990s for the treatment and prevention of osteoporosis in postmenopausal women.

Fosamax treats osteoporosis by correcting an imbalance in the so-called "bone remodeling" process. Throughout a person's life, bones are continuously broken down through a process called resorption and then reformed by the creation of new

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bone cells. In postmenopausal women, the rate of bone resorption exceeds that of bone formation, thereby causing bone loss. If bone loss continues unchecked, a person may develop osteoporosis, "a disease characterized by low bone mass and deterioration of bone structure that causes bone fragility and increases the risk of fracture."² Bisphosphonates like Fosamax slow the resorption process, restoring the balance between resorption and formation and reducing the risk of osteoporotic fracture.

Plaintiffs claim, however, that Fosamax can actually increase the risk of certain bone fractures. They allege that by slowing resorption, bisphosphonates inhibit bone repair. According to Plaintiffs, bones frequently develop so-called "microcracks," which are ordinarily repaired through the resorption process. An accumulation of microcracks can lead to incomplete bone fractures called "stress fractures." The standalone term "stress fracture" typically connotes a fracture resulting from excessive loading of a normal bone, and is commonly seen in physically active individuals. A so-called "insufficiency stress fracture," by contrast, is a fracture caused by normal loading of poor-quality bone. Plaintiffs claim that while stress fractures typically heal on their own, "some Fosamax users who develop insufficiency fractures have reduced bone toughness, and Fosamax prevents the normal repair of the fracture."³ According to Plaintiffs, these patients may then go on to develop what are known as "atypical femoral fractures": severe, non-traumatic, low-energy complete fractures of the femur.

Plaintiffs in this case are all Fosamax users who suffered atypical femoral fractures. They allege, among other things, that (1) Fosamax caused these atypical fractures by slowing the resorption process and allowing microcracks to accumulate, and (2) Merck was aware of the risk of such fractures but acted unlawfully by failing to warn doctors and patients of those dangers. They claim that Merck should have included a warning about atypical femoral fractures in the federally-mandated drug warnings that accompany prescription drugs. The interplay, and potential collision, between state-law warning duties and federal regulatory requirements is the subject of this appeal.

B. Regulatory Framework

The Food, Drug, and Cosmetic Act ("FDCA")⁴ regulates the marketing and sale of prescription drugs in the United States. Under the FDCA, a manufacturer must obtain approval from the United States Food and Drug Administration ("FDA") before marketing a new drug.⁵ As part of a new drug application, the manufacturer must submit a proposed package insert, commonly called the "drug label," that sets out the drug's medical uses ("indications") and health risks.⁶ "To obtain FDA approval, drug companies generally must submit evidence from clinical trials and other testing that evaluate the drug's risks and benefits and demonstrate that it is safe and effective for all of the indications 'prescribed, recommended, or suggested' on the drug's label."⁷ The FDA's

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approval of a new drug application is conditioned on its approval of the exact text of the drug label.⁸

Drug labels includes two sections relevant to this litigation: a "Warnings and Precautions" section and an "Adverse Reactions" section. The Warnings and Precautions section must describe "clinically significant adverse reactions," including any that are "serious even if infrequent."⁹ The Adverse Reactions section requires a description of "the overall adverse reaction profile of the drug based on the entire safety database," including a list of all "undesirable effect[s], reasonably associated with use of a drug."¹⁰

After a drug is approved, the FDA retains the authority to approve or require amendments to the drug's label.¹¹ The fundamental premise of the federal drug labeling scheme, however, is that "manufacturers, not the FDA, bear primary responsibility for their drug labeling at all times."¹² The manufacturer is charged not only "with crafting an adequate label" as an initial matter, but also "with ensuring that its warnings remain adequate as long as the drug is on the market."¹³

A manufacturer can fulfill its responsibility to revise the warnings on a drug label in two ways.

First , the "Changes Being Effected" ("CBE") regulation permits a manufacturer to unilaterally change a drug label to reflect "newly acquired information," subject to later FDA review and approval.¹⁴ Under the CBE regulation, the manufacturer may, upon filing a supplemental application with the FDA, change a label to "add or strengthen a contraindication, warning, precaution, or adverse reaction"; it need not wait for FDA approval.¹⁵ To add a warning to the Warnings and Precautions section through a CBE submission, "there need only be 'reasonable' evidence of a causal association with the drug, a standard that could be met by a wide range of evidence."¹⁶ Thus, a manufacturer can amend the label to...