MOLNAR et al v. MERCK & CO., INC.

Filing 2727

OPINION filed re: 11cv5304. Signed by Judge Joel A. Pisano on 6/27/2013. (mmh)

FOR PUBLICATION
UNITED STATES DISTRICT COURT
DISTRICT OF NEW JERSEY

:
IN RE: FOSAMAX (ALENDRONATE SODIUM) :
PRODUCTS LIABILITY LITIGATION
:
:
_________________________________________ :
:
BERNADETTE GLYNN and RICHARD GLYNN, :
:
Plaintiffs,
:
:
v.
:
MERCK SHARP & DOHME CORP,
:
:
Defendant.
:
:

Civil Action No. 11-5304, 08-08
OPINION

PISANO, District Judge

Plaintiffs Bernadette Glynn and Richard Glynn (“Plaintiffs”) brought this lawsuit against

Defendant Merck, Sharp, & Dohme Corp. (“Defendant”), the manufacturer of Fosamax, which is
a drug approved by the United States Food and Drug Administration (“FDA”) for the treatment
and prevention of osteoporosis. This matter is part of the multi-district litigation (“MDL”)
concerning Fosamax and involves allegations that Fosamax causes atypical femur fractures
(“AFFs 1 ”), it caused Plaintiff Mrs. Glynn’s femur fracture, and Defendant failed to warn
physicians about Fosamax and AFFs. Presently before the Court is Defendant’s Motion for
Summary Judgment based upon Federal Preemption [docket # 25], Motion for Judgment as a
Matter of Law pursuant to Rule 50(a) [docket # 198], Renewed Motion for Judgment as a Matter
of Law pursuant to Rule 50(a) [docket # 209], and Renewed Motion for Judgment as a Matter of

1

The abbreviation of atypical femur fracture (singular) is “AFF.”

1 

Law pursuant to Rule 50(b) [docket # 216]. The issue in these Motions and before the Court is
whether there is clear evidence that the FDA would not have approved a stronger warning to the
Fosamax label, thereby warranting preemption of Plaintiffs’ failure to warn claim. See Wyeth v.
Levine, 555 U.S. 555 (2009). This Court heard oral argument on the federal preemption issue on
March 8, 2013 and reserved decision until a trial record had been established. See Fed. R. Civ.
P. 78. A jury trial took place from April 8, 2013 to April 29, 2013. On April 29, 2013, the jury
returned a verdict for Defendant, finding that Plaintiff did not prove by a preponderance of the
evidence that she experienced an AFF in April 2009. Because the record contains clear evidence
that the FDA would not have approved a stronger warning to the Precautions section of the
Fosamax label, this Court grants the Motions on federal preemption.
I.

BACKGROUND2
A.

Fosamax Approval & Mrs. Glynn’s Fosamax Use

In September 1995, the FDA approved Fosamax for the treatment of osteoporosis in
postmenopausal women, and in April 1997, the FDA approved Fosamax for the prevention of
osteoporosis in postmenopausal women. Since this time, Fosamax has remained FDA approved
for the treatment and prevention of postmenopausal osteoporosis.
In 2002, Dr. Murat Acemoglu first prescribed Fosamax to Mrs. Glynn after diagnosing
her with “osteopenia – osteoporosis” [docket # 27, Confoy Dec., Ex. 27 & 28]. Mrs. Glynn took
Fosamax until April 17, 2009, when she fractured her right femur. Final Pretrial Order ¶ 3.

2

This Background section contains facts that pertain to the federal preemption issue. For a more complete
discussion of the facts of this case, see this Court’s Opinion dated April 11, 2013 [docket # 183].

2 

B.

History of Fosamax Label Change

On June 13, 2008, the FDA contacted Defendant and other bisphosphonate

3

manufacturers and requested any investigations they conducted “regarding the occurrence of
atypical fractures with bisphosphonate use,” any investigational plans, and “all hip and femoral
fracture case reports” they received [docket # 26, Declaration of Karen A. Confoy in Support of
the Motion for Summary Judgment and Motion for Summary Judgment Based Upon Federal
Preemption (“Confoy Dec.”), Ex. 5; docket # 27, Confoy Dec., Ex. 4]. The FDA also asked that
Defendant and the other bisphosphonate manufacturers make an effort where possible “to clarify
the fracture location and the duration of bisphosphonate exposure for all case reports.” Id. The
FDA explained that it was “aware of reports regarding the occurrence of subtrochanteric hip
fractures in patients using bisphosphonates” and is “concerned about this developing safety
signal.” Id.
On July 18, 2008, Defendant responded to the FDA’s request and included summary
tables of clinical and post-marketing data, clinical Council for International Organizations of
Medical Sciences (“CIOMS”) reports, and post-marketing CIOMS reports [docket # 27, Confoy
Dec., Ex. 6]. The FDA’s review of this data as well as the data from other bisphosphonate
manufacturers “did not show an increase in . . . [the risk of atypical subtrochanteric femur
fractures] in women using these medications” [docket # 26, Confoy Dec., Ex. 7].
On September 15, 2008, Defendant submitted a Prior Approval Supplement (“PAS”) to
the FDA, proposing “to add language to both the Precaution[s] and Adverse Reactions/PostMarketing Experience section[s] of the label to describe low-energy” subtrochanteric femoral

3

Fosamax belongs to a class of drugs known as bisphosphonates.

3 

fractures [docket # 27, Confoy Dec., Ex. 8]. Defendant explained that “[i]t is not possible with
the present data to establish whether treatment with” Fosamax “increases the risk of [these] . . .
low-energy subtrochanteric and/or proximal shaft fractures,” but because there is a temporal
association between these fractures and Fosamax, Defendant thought that it was “important to
include an appropriate statement about them in the product label.” Id. Defendant sought to add
the following language to the Precautions section of the label:
Low-Energy Femoral Shaft Fracture
Low-energy fractures of the subtrochanteric and proximal femoral
shaft have been reported in a small number of bisphosphonatetreated patients. Some were stress fractures (also known as
insufficiency fractures) occurring in the absence of trauma. Some
patients experienced prodromal pain in the affected area, often
associated with imaging features of stress fracture, weeks to
months before a complete fracture occurred. The number of
reports of this condition is very low, and stress fractures with
similar clinical features also have occurred in patients not treated
with bisphosphonates. Patients with suspected stress fractures
should be evaluated, including evaluation for known causes and
risk factors (e.g., vitamin D deficiency, malabsorption,
glucocorticoid use, previous stress fracture, lower extremity
arthritis or fracture, extreme or increased exercise, diabetes
mellitus, chronic alcohol abuse), and receive appropriate
orthopaedic care. Interruption of bisphosphonate therapy in
patients with stress fractures should be considered, pending
evaluation of the patient, based on individual benefit/risk
assessment.
[Id.]
Additionally, Defendant proposed adding “low-energy femoral shaft fracture” to the Adverse
Reactions/Post-Marketing Experience section of the label and the following statement to the
Patient Package Insert: “Patients have experienced fracture in a specific part of the thigh bone.
Call your doctor if you develop new or unusual pain in the hip or thigh.” Id.

4 

On April 15, 2009, an FDA representative e-mailed Defendant and stated that the
proposed label change to the Adverse Reactions/Post-Marketing Experience section of the label
would be approved but the label change to the Precautions section would not be approved
[docket # 101, Cecchi Dec., Ex. 83; docket # 27, Confoy Dec., Ex. 10]. Two days later, Mrs.
Glynn fractured her femur.
On May 22, 2009, one month after Mrs. Glynn’s fracture, the FDA formally responded to
Defendant’s proposed label change, recommending that it add “low energy femoral shaft and
subtrochanteric fractures” to the Adverse Reactions/Post-Marketing Experience section of the
label; however, the FDA did not approve the label change to the Precautions section [docket #
27, Confoy Dec., Ex. 11]. Moreover, the FDA warned that Fosamax “may be considered to be
misbranded under the Federal Food, Drug, and Cosmetic Act if [it is] . . . marketed with” these
label changes “before [FDA] approval . . . .” Id.
On July 2, 2009, Defendant submitted to the FDA a Changes Being Effected (“CBE”)
supplement to add information about femur fractures to the Adverse Reactions/Post-Marketing
Experience section of the label because the FDA told Defendant that submitting a CBE
supplement was the “quickest route to update the [Product Circular] PC” for Fosamax [docket #
27, Confoy Dec., Ex. 12]. On March 1, 2010, the FDA approved the CBE supplement [docket #
26, Confoy Dec., Ex. 9].
On March 10, 2010, the FDA issued a Drug Safety Communication, in which it stated
that “[a]t this point, the data that FDA has reviewed have not shown a clear connection between
bisphosphonate use and a risk of atypical subtrochanteric femur fractures” [docket # 26, Confoy
Dec., Ex. 5]. The FDA did state, however, that it was “working closely with outside experts,

5 

including members of the . . . American Society of Bone and Mineral Research Subtrochanteric
Femoral Fracture Task Force, to gather additional information that may provide more insight into
this issue.” Id.
On September 14, 2010, the American Society for Bone and Mineral Research
(“ASBMR”) published an article entitled Atypical Subtrochanteric and Diaphyseal Femoral
Fractures: Report of a Task Force of the American Society for Bone and Mineral Research
[docket # 26, Confoy Dec., Ex. 13]. 4 The report stated that although there is an association
between long-term bisphosphonate use and AFFs, the association has “not been proven to be
causal.” Id. at 2269, 2287. The report concluded that although AFFs are rare, “they appear to be
more common in patients who have been exposed to long-term BPs [(“bisphosphonates”)],
usually for more than 3 years . . . .” Id. at 2287. The report further provided that although “BPs
are important drugs for the prevention of common osteoporotic fractures,” “atypical femoral
fractures are of concern, and more information is urgently needed both to assist in identifying
patients at particular risk and to guide decision making about duration of BP therapy. Physicians
and patients should be made aware of the possibility of atypical femoral fractures and of the
potential for bilaterality through a change in labeling of BPs.” Id.

4

 In this report, the ASBMR defined AFF by listing its Major Features, which are required to satisfy the definition of
AFF, and Minor Features, which may be associated with AFFs but are not required characteristics of them [docket #
26, Confoy Dec., Ex. 13]. The Major Features of an AFF are: (1) that it is “located anywhere along the femur from
the distal to the lesser trochanter to just proximal to the supracondylar flare”; (2) “associated with no trauma or
minimal trauma, as in a fall from a standing height or less”; (3) transverse or short oblique configuration; (4)
noncomminuted; and (5) complete fractures extend through both cortices and may be associated with a medial spike,
incomplete fractures involve only the lateral cortex. Id. The Minor Features of an AFF are: (1) localized periosteal
reaction of the lateral cortex; (2) generalized increase in cortical thickness of the diaphysis; (3) prodromal symptoms
such as dull or aching pain in the groin or thigh; (4) bilateral fractures and symptoms; (5) delayed healing; (6)
comorbid conditions (e.g., vitamin D deficiency, rheumatoid arthritis, hyposphosphotasia); and (7) use of
pharmaceutical agents (e.g., bisphosphonates, glucocorticoids, and proton pump inhibitors). Id.

6 

The FDA responded to the report by issuing a Drug Safety Communication, in which it
stated “[a]lthough it is not clear if bisphosphonates are the cause [of AFFs], these unusual femur
fractures have been identified in patients taking these drugs” [docket # 26, Confoy Dec., Ex. 14].
Additionally, the FDA informed that the “optimal duration of bisphosphonate treatment for
osteoporosis is unknown” but “clinical trial data . . . support[s] effectiveness for the reduction of
common bone fractures for three to five years.” Id. Regarding the ASBMR Task Force’s
recommendation of a label change, the FDA stated that it “has assembled and is thoroughly
reviewing all long term data available on the products, as well as all safety reports, and is
considering label revisions.” Id. (emphasis added).
In October 2010, the FDA issued another Drug Safety Communication, informing that it
would require all bisphosphonate manufacturers to add information on AFFs to the Precautions
section of the drug labels and require a new Limitations of Use statement in the Indications and
Usage section of the label because “these atypical fractures may be related to long-term . . .
bisphosphonate use” [docket # 26, Confoy Dec., Ex. 15]. It reiterated that “[a]lthough it is not
clear if bisphosphonates are the cause, these unusual femur fractures have been predominantly
reported in patients taking bisphosphonates.” Id. On January 11, 2011, Defendant submitted the
agreed upon label changes to the FDA [docket # 27, Confoy Dec., Ex. 18]. Also in January
2011, the FDA issued an update on femur fractures and bisphosphonate use, stating “[a]lthough
it is not clear that the drugs are a direct cause of these unusual fractures, they have mainly been
reported in patients taking bisphosphonates” [docket # 26, Confoy Dec., Ex. 19].
Currently, the Fosamax label includes the following language: “Atypical, low-energy, or
low trauma fractures of the femoral shaft have been reported in bisphosphonate-treated patients.
. . . Causality has not been established as these fractures also occur in osteoporotic patients who
7 

have not been treated with bisphosphonates. Atypical femur fractures most commonly occur
with minimal or no trauma to the affected area” [docket # 26, Confoy Dec., Ex. 20].
C.

Procedural History

On September 15, 2011, Plaintiffs filed a Complaint in this Court against Defendant,
alleging causes of action for: (1) failure to warn; (2) defective design; (3) negligence; (4)
negligent misrepresentation; (5) breach of express warranty; (6) breach of implied warranty of
fitness for a particular purpose; (7) breach of implied warranty of merchantability; (8) violation
of the Consumer Fraud Act, N.J.S.A. 56:8-2 et seq.; (9) violations of the New York General
Business Law, N.Y. Gen. Bus. Law §§ 349 et seq. and 350 et seq.; (10) unjust enrichment; (11)
punitive damages pursuant to the New Jersey Product Liability Act, N.J.S.A. 2A:58C-1 et seq.,
and the New Jersey Punitive Damages Act, N.J.S.A. 2A:15-5.10, et seq.; and (12) loss of
consortium on behalf of Plaintiff Richard Glynn [docket # 1]. 5 Defendant moved for summary
judgment based on federal preemption on January 15, 2013, arguing that Plaintiffs’ claims, all of
which ultimately concern a failure to warn, are preempted because the FDA rejected Defendant’s
proposed label change and this constitutes clear evidence that the FDA would not have approved
a stronger warning to the Precautions section of the label [docket #25]. On March 8, 2013, the
Court heard argument on the preemption issue and reserved decision on it [docket # 138]. On
April 2, 2013, the Court reserved decision on the federal preemption motion until there was a
complete trial record in the case [docket # 156].

5

Subsequently, Plaintiffs decided to pursue only the following claims: (1) failure to warn; (2) breach of the implied
warranty of fitness for a particular purpose; (3) violations of the New York General Business Law; and (4) punitive
damages. The Court granted summary judgment on the New York General Business Law claims [docket # 183]. In
addition, the Court granted a Motion for Judgment as a Matter of Law as to the breach of implied warranty of fitness
for a particular purpose claim and punitive damages [docket # 198]. Trial Tr. 1896:2-17; 2586:20-22. Thus, the
failure to warn claim is the only claim that remains. Trial Tr. 2586:11-12.

8 

Trial began on April 8, 2013 and concluded on April 29, 2013. After the close of the
Plaintiff’s case, on April 20, 2013, Defendant filed a Motion for Judgment as a Matter of Law
pursuant to Federal Rule of Civil Procedure 50(a) [docket # 198]. Defendant argued that
although it submitted to the FDA all the information relevant to a label change and tried to
change the Precautions section of the label to include low-energy femoral fractures, the FDA
rejected the label change. On April 26, 2013, Defendant renewed its Motion for Judgment as a
Matter of Law, again arguing that Plaintiffs’ claims are preempted because Defendant proposed a
change to the Precautions section of the Fosamax label and the FDA rejected it [docket # 209].
On April 29, 2013, the jury returned a verdict for Defendant, finding that Plaintiffs did not prove
by a preponderance of the evidence that Mrs. Glynn experienced an AFF in April 2009. The
following day, the Court held an in-person status conference to discuss the preemption issue as
well as other MDL issues. The Court explained that it previously deferred decision on the
preemption issue for “a complete record” and “the best way to do that was to try the” case.
Hearing Tr., 6:10-14, April 30, 2013. Although Plaintiffs had several opportunities to present
evidence on preemption, they requested additional time to present more evidence on the issue.
The Court gave Plaintiffs twenty-one days to submit “proposed fact findings that are based upon
the record in opposition to” the preemption motions. Id. at 19:24-20:1. Thereafter, on May 6,
2013, Defendant submitted a Renewed Motion for Judgment as a Matter of Law pursuant to Rule
50(b) [docket # 216]. Plaintiffs submitted an opposition brief and Defendant submitted a reply
brief.

9 

II.

DISCUSSION
A.

Standard

“If a court does not grant a motion for judgment as a matter of law made under Rule
50(a), the court is considered to have submitted the action to the jury subject to the court’s later
deciding the legal questions raised by the motion.” Fed. R. Civ. P. 50(b). The movant may then
file a renewed motion for judgment as a matter of law, and in “ruling on the renewed motion, the
court may: (1) allow judgment on the verdict, if the jury returned a verdict; (2) order a new trial;
or (3) direct the entry of judgment as a matter of law.” Id.
B.

Plaintiffs’ Claims Are Preempted

Defendant argues that Plaintiffs’ claims are preempted under federal law because it
proposed a label change to the Precautions section of the Fosamax label to include a warning
about low-energy femur fractures, and the FDA rejected the label change after Mrs. Glynn’s
fracture. Defendant asserts that this constitutes clear evidence that the FDA would have rejected
any warning about these fractures prior to Mrs. Glynn’s femur fracture. Moreover, Defendant
contends that Plaintiffs’ claims are preempted for three additional reasons: (1) Plaintiffs did not
present evidence that the FDA rejected the proposed label change for using the phrase “stress
fracture” as opposed to AFF; (2) Plaintiffs did not show that the label change could have been
successfully presented through a CBE supplement; and (3) Plaintiffs did not show that Defendant
withheld any information from the FDA.
Plaintiffs, however, argue that Defendant has not shown clear evidence that the FDA
would have rejected language about AFFs in the Precautions section of the Fosamax label prior
to Mrs. Glynn’s fracture. Plaintiffs assert that preemption is improper for the following reasons:
10 

(1) the FDA rejected the PAS because Defendant used the phrase “stress fracture” instead of
“atypical” fracture, and the FDA would have approved an appropriately worded warning; (2)
Defendant could have changed the label through a CBE supplement; (3) Defendant did not
provide all of the information it had on femur fractures and Fosamax to the FDA, and had it done
so, the FDA would have approved a properly worded warning in 2008; and (4) Defendant failed
to warn the FDA as soon as there was reasonable evidence of a causal association between
Fosamax and AFFs.
Defendant submitted a reply brief, again arguing that preemption is proper because
Defendant proposed a label change in 2008 and the FDA rejected it in 2009, after Mrs. Glynn’s
fracture. Defendant asserts that the FDA did not reject the label change because Defendant used
the phrase “stress fracture” since references to “stress fractures” were included to aid in the early
identification of low-energy femur fractures. Moreover, Defendant contends that it did not fail to
submit information to the FDA.

Lastly, Defendant points out that the evidence Plaintiffs

presented in their brief was not introduced at trial and thus, is not properly before this Court on
this Motion; even if it was properly before this Court, the evidence does not change the fact that
clear evidence exists that the FDA would not have approved a stronger warning to the Fosamax
label.
The Supremacy Clause provides that the “Constitution, and Laws of the United States . . .
shall be the supreme Law of the Land . . . .” U.S. Const. art. VI, cl. 2. It “invalidates state laws
that interfere with, or are contrary to, federal law.” Hillsborough County, Florida v. Automated
Medical Laboratories, Inc., 471 U.S. 707, 712 (1985) (internal quotation omitted). Federal law
preempts state law in three ways: (1) express preemption; (2) field preemption, and (3) conflict
preemption. Farina v. Nokia Inc., 625 F.3d 97, 115 (3d Cir. 2010), cert. denied, 132 S.Ct. 365
11 

(2011); Dobbs v. Wyeth Pharmaceuticals, 797 F. Supp. 2d 1264, 1268 n.3 (W.D. Okla. 2011).
Express preemption occurs when Congress states “in express terms” that it is preempting state
law. Hillsborough County, Florida, 471 U.S. at 713. Field preemption occurs when Congress
intends to preempt state law “in a particular area” or in other words “the scheme of federal
regulation is sufficiently comprehensive . . . [so] Congress ‘left no room’ for supplementary state
regulation.” Id. Conflict preemption is when a “state law is in actual conflict with federal law”;
this exists “where it is impossible for a private party to comply with both state and federal
requirements . . . or where state law stands as an obstacle to the accomplishment and execution
of the full purposes and objectives of Congress.” Sprietsma v. Mercury Marine, a Div. of
Brunswick Corp., 537 U.S. 51, 64 (2002) (internal quotation omitted). This case concerns
conflict preemption because Defendant argues that it was impossible to comply with the state
law duty to warn and the FDA’s regulations6 since Plaintiffs argue that a warning about lowenergy femur fractures should have been included in the Fosamax label but the FDA rejected a
proposed warning.
Conflict preemption, however, “is a demanding defense.” Wyeth, 555 U.S. at 573. As a
result, generally, FDA approval or compliance with FDA labeling regulations is not a complete
defense to a state failure to warn claim. Id. at 559. If, however, there is “clear evidence that the
FDA would not have approved a change” to the prescription drug’s label, then it is impossible to
comply with both federal and state requirements 7 and the state failure to warn claim is

6

 Federal regulations “preempt state laws in the same fashion as congressional statutes.” Farina, 625 F. 3d at 115
(citing Fid. Fed. Sav. & Loan Ass’n v. de la Cuesta, 458 U.S. 141, 153 (1982)).
7

Federal regulations require that a drug’s label “be revised to include a warning about a clinically significant hazard
as soon as there is reasonable evidence of a causal association with a drug; a causal relationship need not have been
definitely established.” 21 C.F.R. § 201.57.

12 

preempted. Id. at 571. Wyeth does not define “clear evidence,” so “application of the clear
evidence standard is necessarily fact specific.” Dobbs, 797 F. Supp. 2d at 1270.
Here, 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 Mrs. Glynn’s
fracture. In September 2008, Defendant submitted a PAS to the FDA, seeking to add language
about low-energy femur fractures to the Precautions and Adverse Reactions sections of the label.
In May 2009, approximately one month after Mrs. Glynn’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 Mrs.
Glynn’s injury. See Robinson v. McNeil Consumer Healthcare, 615 F.3d 861, 873 (7th Cir.
2010) (finding clear evidence that the FDA would not have approved a label change because the
FDA did not approve “a reference to SJS/TEN on the label of over-the-counter drugs containing
ibuprofen, when it had been asked to do so in a submission”); Dobbs, 797 F. Supp. 2d at 1276-77
(finding clear evidence that the FDA would have rejected an expanded warning for Effexor after
the FDA rejected the warning added by Defendant); see also Wyeth, 555 U.S. at 571-72 (holding
that Wyeth “failed to demonstrate that it was impossible for [it] . . . to comply with both federal
and state requirements” and reasoning that it “offered no such evidence” and never argued “that
it attempted to give” a warning but “was prohibited from doing so by the FDA”).
Indeed, the evidence presented at trial establishes that the FDA would not have approved
a label change to the Precautions section of the Fosamax label prior to Mrs. Glynn’s injury. In
fact, Dr. Cheryl Blume (“Dr. Blume”), one of Plaintiffs’ experts who was “central” to Plaintiffs’
preemption analysis, testified that the FDA “rejected” Defendant’s PAS. Hearing Tr., 12:2413 

13:13, April 2, 2013; Trial Tr., 661:10-14.

Moreover, Dr. Lisa Rarick (“Dr. Rarick”), one of

Defendant’s experts who worked for the FDA for fifteen years, testified that the FDA “rejected a
precaution” to the Fosamax label in their May 22, 2009 letter to Defendant. Trial Tr., 2436:2224; 2501:7-9. Dr. Rarick further testified that although the FDA had the authority to ask
Defendant to submit “alternative precautionary language” if it was “still contemplating [that]
they might accept a precaution,” the FDA did not do so, thereby indicating that it would not
accept a label change to the Precautions section of the Fosamax label at that time. Id. at
2501:10-2502:1. Furthermore, Dr. Rarick testified that the FDA had the authority to request that
Defendant “make a label change to include reports of low-energy spontaneous subtrochanteric or
atypical femur fractures,” but they never made such a request. Id. at 2485:4-8; 2578:2-12. Thus,
clear evidence exists that the FDA would not have approved a label change to the Precautions
section of the Fosamax label prior to Mrs. Glynn’s fracture because Defendant submitted a label
change and the FDA rejected it, and the FDA never required Defendant to submit new language
or change the label, which demonstrates that the FDA did not think that the label should have
been changed at that time.
Plaintiffs did not present any evidence at trial to refute preemption. First, Plaintiffs did
not offer any evidence that Defendant’s PAS was rejected due to language, specifically the use of
“stress fracture” instead of “AFF,” or that the FDA would have approved a properly worded
label change. Instead, it would have been improper for Defendant to use the term “AFF” in 2008
when they submitted the PAS because, as Dr. Blume testified, the phrase “atypical femur
fractures . . . wasn’t even contrived until 2010 or 2011.” Id. at 725:22-24. In addition, Dr.
Cornell, the Clinical Director of Orthopaedic Surgery at the Hospital for Special Surgery and one
of Plaintiffs’ experts, explained that Fosamax “can lead to . . . subsequent stress fracture
14 

formation,” and when he wrote about these fractures, he was “talking about atypical femur
fractures.” Id. at 1264:20-1265:8. Moreover, Dr. Rarick testified that in rejecting Defendant’s
PAS, the FDA did not conclude that the label was “confusing to doctors” or that “stress fractures
didn’t look as severe and significant as . . . atypical femur fractures”; instead, Dr. Rarick stated
that the FDA rejected the PAS because the “data didn’t support the precaution language.” Id. at
2512:10-18.

This testimony demonstrates that the FDA did not reject the PAS due to

Defendant’s use of the phrase “stress fracture.” Not only was the phrase AFF not coined in
2008, but some doctors used “stress fracture” as a term to refer to low-energy subtrochanteric
fractures.
Second, Plaintiffs did not offer any evidence that Defendant could have submitted a CBE
supplement to change the Precautions section of the Fosamax label. A CBE supplement gives a
“manufacturer . . . the ability to change the label without FDA approval.” Mason v. SmithKline
Beecham Corp., 596 F.3d 387, 392 (7th Cir. 2010); Dobbs, 797 F. Supp. 2d at 1271 (citing 21
C.F.R. § 314.70(c)(6)(iii)) (stating it is “an exception to the requirement of advance approval for
label changes under certain circumstances”). A CBE supplement “allows a pre-approval label
change by the manufacturer where the change is needed to add or strengthen a contraindication,
warning, precaution or information about an adverse reaction.” Dobbs, 797 F. Supp. 2d at 1271
(citing 21 C.F.R. § 314.70(c)(6)(iii)(A)). Like a PAS, the “proposed change must be based on
‘reasonable evidence of’ an association between a hazard and the drug at issue; however, a
causal relationship need not have been definitely established.”

Id. (citing C.F.R. §

201.57(c)(6)(i)). After the label change has been affected, the “FDA has the opportunity to
consider whether or not it will accept the change.” Mason, 586 F.3d at 392. Drs. Blume and
Rarick testified that if the FDA rejects a CBE label change, the manufacturer must change the
15 

label, otherwise it will be misbranded. Trial Tr. 733:16-734:9; 2502:8-16. Thus, since the FDA
rejected Defendant’s PAS, it would not have approved a CBE seeking to add the same language
to the label that it just rejected in the PAS, and any changes Defendant made using the CBE
supplement would cause the drug to be misbranded. In addition, Dr. Rarick testified that the
FDA could have requested that Defendant submit the label change using the CBE instead of the
PAS method, but the FDA did not do so. Id. at 2489:19-22. Moreover, Dr. Rarick opined that
the CBE method was not “the appropriate method to submit” a label change regarding lowenergy subtrochanteric femur fractures because this “topic . . . was under FDA’s review . . . .”
Id. at 2493:11-22. As a result, the evidence does not show that Defendant could have changed
the Precautions section of the Fosamax label using a CBE supplement.
Third, Plaintiffs did not show that Defendant failed to provide all the information it had
on femur fractures to the FDA and that Defendant failed to warn the FDA as soon as there was
reasonable evidence of a causal association between Fosamax and AFFs. Instead, Dr. Blume and
Dr. Santora, Defendant’s employee who is responsible for Fosamax, testified that Defendant
supplied the Odvina report, Goh report, Adverse Event Reports, and data it obtained from
physicians; Defendant also submitted information when the FDA requested it in 2008. Id. at
729:5-730:21; 2175:16-21; 2176:4-10; 2254:15-19; 2261:13-2262:8. Regarding the timing of
Defendant’s proposed label change, there is no evidence that Defendant failed to submit the label
change when it had reasonable evidence of a causal association between Fosamax and femur
fractures. Defendant submitted the PAS three months after the FDA requested information from
bisphosphonate manufacturers, and as late as March 2010, the FDA did not see a “clear
connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures”
[docket # 26, Confoy Dec., Ex. 5].
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Not only did Plaintiffs fail to offer any evidence at trial to refute preemption but the
exhibits Plaintiffs cited in their opposition brief were not presented at trial [docket # 218]. This
is inappropriate on a Motion for Judgment as a Matter of Law where “the court is limited to the
trial record and nothing else.” Laymon v. Lobby House, Inc., 613 F. Supp. 2d 504, 510 (D. Del.
2009). Even if the evidence Plaintiffs cited were part of the trial record, this Court is not
persuaded that it would change the fact that there is clear evidence that the FDA would not have
approved a stronger warning prior to Mrs. Glynn’s fracture.
Therefore, preemption is warranted in this case. Defendant submitted a PAS in 2008
seeking to change the Precautions section of the Fosamax label to include information on lowenergy subtrochanteric femur fractures, but the FDA rejected the PAS in May 2009, one month
after Mrs. Glynn’s fracture. This constitutes clear evidence that the FDA would not have
approved a stronger warning prior to Mrs. Glynn’s fracture. Although Plaintiffs have had several
opportunities to introduce evidence in opposition to preemption, they have not refuted the fact
that clear evidence exists. Consequently, based on the record before the Court, Plaintiffs’ failure
to warn claim is preempted.
III.

CONCLUSION

For the reasons outlined above, this Court grants Defendant’s Motion for Summary
Judgment based upon Federal Preemption [docket # 25], Motion for Judgment as a Matter of
Law [docket # 198], second Motion for Judgment as a Matter of Law [docket # 209], and
Renewed Motion for Judgment as a Matter of Law [docket # 216] and enters judgment in favor
of Defendant. An appropriate Order accompanies this Opinion.
Dated: June 27, 2013

/s/ Joel A. Pisano
JOEL A. PISANO, U.S.D.J.
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