In Re: Taxotere (Docetaxel) Eye Injury Products Liability Litigation

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UNITED STATES DISTRICT COURT
EASTERN DISTRICT OF LOUISIANA
IN RE: TAXOTERE (DOCETAXEL) 	) 	MDL NO. 3023
EYE INJURY 	)
PRODUCTS LIABILITY LITIGATION 	)
)
This document relates to: 	) 	SECTION: “H” (5)
All cases 	)
ORDER AND REASONS
Before the Court is Sanofi’s Motion for Summary Judgment Based on
Preemption (Doc. 445). For the following reasons, Sanofi’s Motion for Summary
Judgment Based on Preemption is DENIED.
BACKGROUND
Plaintiffs 	in 	this 	multidistrict 	litigation 	(“MDL”) 	are 	suing 	several
pharmaceutical 	companies 	that 	manufactured 	and/or 	distributed 	a
chemotherapy drug, Taxotere or docetaxel, that Plaintiffs were administered
for the treatment of cancer.1 Among these companies are Defendants Sanofi
U.S. Services Inc. and sanofi-aventis U.S. LLC and (collectively, “Sanofi”).
I. 	Alleged Injury
Plaintiffs allege that Taxotere or docetaxel caused them to sustain
injuries 	to 	their 	lacrimal 	systems, 	including 	punctal, 	canalicular, 	and/or
nasolacrimal duct stenosis, which resulted in excessive tearing, otherwise
known as epiphora.
1 Taxotere is the brand name for the drug docetaxel.
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While it has undergone certain revisions, as of 2002, Sanofi’s label has
warned about “excessive tearing which may be attributable to lacrimal duct
obstruction.” Plaintiffs allege that Sanofi failed to warn them that stenosis is
a common but preventable side effect, and that Sanofi’s label “has never
identified stenosis as a cause of excessive tearing or warned of the rapid onset
at which stenosis can occur, the potentially irreversible nature of the injury, or
the urgent need to provide treatment and refer patients to a lacrimal specialist
at the first sign of excessive tearing.”2 They allege that early referral could
have prevented the progression to permanent stenosis. They further contend
that while epiphora in some Plaintiffs may have fully or partially resolved,
Plaintiffs 	are 	often 	left 	with 	scarring, 	disfigurement, 	and 	sometimes
permanent tubes in their ducts.
Plaintiffs allege that the mechanism of the injury at issue occurs through
secretion of Taxotere/docetaxel in the tears causing inflammation, scarring,
and/or 	fibrosis 	in 	the 	lacrimal 	drainage 	system 	and 	that 	the 	punctal,
canalicular, and sometimes nasolacrimal duct are predominately affected.3
Dr. Bita Esmaeli (Sanofi’s proposed expert and ophthalmic plastic and
orbital surgeon) and Dr. Vikram Durairaj (Plaintiffs’ proposed expert and
2 Doc. 25 at 7.
3 Dr. Esmaeli opines that “[a]lthough I have hypothesized that stenosis/obstruction
may develop due to secretion of docetaxel in the tear film and we have demonstrated the
presence 	of 	docetaxel 	in 	the 	tear 	samples 	collected 	from 	patients 	24 	hours 	after
administration of the drug, the exact mechanism of this side effect is not proven and may be
multifactorial.” Doc. 445-27 at 22.
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oculoplastic and orbital surgeon) explain the injury at issue in detail.4 Dr.
Esmaeli provides the following illustration of the relevant ocular anatomy.5
The 	lacrimal 	drainage 	system 	comprises 	four 	main 	anatomical
structures: the punctum, canaliculus, lacrimal sac, and the nasolacrimal duct.
After tears are released from the lacrimal gland, the eye’s drainage system
functions through gravity and a blinking-induced pumping mechanism, which
together move tears from the eye into the nose. The tears first flow from the
surface of the eye though the puncta. Each eye has an upper punctum and
lower punctum. The puncta then lead to the canaliculi, which are narrow tubes
that drain into the lacrimal sac. Inferiorly, the lacrimal sac is continuous with
4 Doc. 445-27 (Report of Dr. Esmaeli), Doc. 493-103 (Report of Dr. Durairaj).
5 Doc. 445-27 at 4. Dr. Durairaj also provides illustrations in his Report. Doc. 493-103
at 6, 7.
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the nasolacrimal duct, which opens into the nose under the inferior turbinate.
The tears are then absorbed by the body.
Dr. Durairaj explains that there is a distinct lacrimal secretory system
and 	a 	nasolacrimal 	excretory 	system. 	The 	secretory 	lacrimal 	system 	is
responsible 	for 	the 	production 	of 	tears, 	while 	the 	“nasolacrimal 	system
excretory apparatus” is responsible for the drainage of tears, as described
above. He opines that excessive tearing can be caused by a problem in either
of these two systems, and that it is important to distinguish between “excessive
production of tears . . . in the secretory lacrimal system” and the “inability to
drain tears in the 	excretory nasolacrimal system” because often, in this
context, the former “will resolve once treatment is over whereas stenosis of the
nasolacrimal drainage system does not.”6
There are a few procedures used to determine the presence/location of
stenosis. One is probing (sometimes with irrigation), which involves inserting
a metal probe through the punctum and advancing it through the canaliculi
and into the lacrimal sac. If irrigation is performed, saline is injected into the
nasolacrimal drainage system. Another is the “dye disappearance test,” which
involves administering dyed drops into the eye and examining how the dye
drains.
According 	to the 	parties’ experts, 	treatment 	of stenosis 	(which Dr.
Durairaj refers to as scarring and/or narrowing) depends on its anatomic
location and severity. For example, stenosis of the punctum may be first
treated 	with 	probing 	and 	irrigation 	and 	topical 	steroids. 	If 	these 	are
6 Doc. 493-103 at 8.
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unsuccessful, stenosis may be treated via punctoplasty, a surgical procedure
intended to widen or open the puncta to restore drainage. A small stent may
also be inserted temporarily to keep the puncta open.
Mild stenosis of the canaliculi and/or nasolacrimal duct is often treated
with probing and irrigation, artificial tears, and/or topical steroids. Moderate
stenosis of the canaliculi and/or nasolacrimal duct is often treated through
bicanalicular 	silicone 	intubation, 	a 	surgical 	intervention 	involving 	the
placement of a silicone stent through the canaliculi of both the upper and lower
eyelids, passing through the nasolacrimal duct, and into the nasal cavity. For
severe stenosis of the canaliculi and/or nasolacrimal duct, there are a number
of surgical procedures. One is dacryocystorhinostomy (“DCR”), a surgical
procedure intended to create a new tear drainage pathway to allow tears to
drain directly into the nasal cavity, after which temporary silicone stents are
inserted to keep the new passage open during healing. DCR may be performed
externally or endoscopically.
Complete and/or severe closure of the canaliculi may require a “total
bypass procedure” involving placement of a permanent Pyrex glass tube, or
“Jones tube,” through an opening inside the corner of the eye and into the
opening in the nasal cavity to drain tears in the nose.7
II. 	Statutory and Regulatory Background
Under the Federal Food, Drug, and Cosmetic Act (“FDCA”), a drug
manufacturer must obtain approval from the Food and Drug Administration
7 	Doc. 	445-27 	at 	31, 	Doc. 	493-103. 	This 	is 	known 	as 	a
“conjunctivodacryocystorhinostomy,” or “CDCR.” Doc. 445-27 at 31. Dr. Durairaj also
describes a surgical procedure called canaliculodacryocystorhinostomy, a reconstructive
procedure used to connect the canaliculus to the lacrimal sac. Doc. 493-103 at 16.
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(“FDA”) before selling its drug in the United States.8 The FDCA lays out
several methods of approval.9 Pursuant to § 505(b)(1), a manufacturer seeking
approval of the first drug of a specific kind, or reference listed drug (“RLD”),
must submit a New Drug Application (“NDA”) containing, “inter alia, ‘full
reports of investigations which have been made to show whether such drug is
safe for use and whether such drug is effective in use.’”10
A. 	Labeling requirements
“The FDA regulates the safety information that appears on the labels of
prescription drugs that are marketed in the United States.”11 “FDA regulations
set out requirements for the content, the format, and the order of the safety
information on the drug label.”12 The Supreme Court has explained that under
the 	FDCA 	and 	its 	corresponding 	regulations, 	a 	drug 	manufacturer 	has
“responsibility for the content of its label at all times.”13 “It is charged both
8 Hickey v. Hospira, 102 F.4th 748, 750 (5th Cir. 2024) (citing 21 U.S.C. § 355(a)).
9 See id. at 751.
10 Id. at 750–51 (quoting 21 U.S.C. § 355(b)(1)(A)(i)). The Fifth Circuit and the parties
refer to this provision and its counterparts—§§ 505(b)(2) and (j)—by their location in the
FDCA rather than their location in the United States Code. Id. at 760 n.1.
11 Merck Sharp & Dohme Corp. v. Albrecht, 587 U.S. 299, 304 (2019) (citing 21 U.S.C.
§ 355(b)(1)(F); 21 C.F.R § 201.57). This “FDA approved prescribing information” is referred
to as the “United States Package Insert, or ‘USPI.’” Doc. 445-4 at 6. As the Supreme Court
has explained, although a drug’s label is commonly understood to refer to the sticker affixed
to the bottle, “in this context the term refers more broadly to the written material that is sent
to the physician who prescribes the drug and the written material that comes with the
prescription bottle when the drug is handed to the patient at the pharmacy.” Albrecht, 587
U.S. at 303–04 (citation modified). These inserts are often lengthy and contain detailed
information about the drug’s medical uses and health risks. Id.
12 Albrecht, 587 U.S. at 304.
13 Wyeth v. Levine, 555 U.S. 555, 570–71 (2009).
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with crafting an adequate label and with ensuring that its warnings remain
adequate as long as the drug is on the market.”14
In 2006, the FDA issued a Final Rule amending 21 C.F.R. §§ 201.56 and
201.57 to set forth the requirements for the content and format of labeling for
human 	prescription 	drugs 	and 	biological 	products.15 	Pursuant 	to 	the
regulations, “[l]abels must include various types of information, organized in a
specific 	manner, 	by 	sections.”16 	“As 	those 	requirements 	make 	clear, 	the
category in which a particular risk appears on a drug label is an indicator of
the likelihood and severity of the risk.”17 “The hierarchy of label information is
designed to ‘prevent overwarning’ so that less important information does not
‘overshadow’ more important information.”18
Two 	sections 	of 	the 	label 	are 	relevant 	here: 	the 	“Warnings 	and
Precautions” section, described in § 201.57(c)(6), and the “Adverse Reactions”
section, discussed in § 201.57(c)(7). “In the Warnings and Precautions section,
14 Id. at 571.
15 Final Rule, Requirements on Content and Format of Labeling for Human
Prescription Drug and Biological Products, 71 Fed. Reg. 3,922 (Jan. 24, 2006) (codified at 21
C.F.R. §§ 201.56, 201.57). This Rule is known as the Physician’s Labeling Rule, or “PLR.” See
U.S. ex rel. Polansky v. Pfizer, Inc., 822 F.3d 613, 616 n.7 (2d Cir. 2016); see also Doc. 445-4
at 6. In the PLR, the FDA stated that “older drugs not subject to the revised labeling content
and format requirements in § 201.57 remain subject to labeling requirements at former §
201.57, which is redesignated as § 201.80 by this final rule,” and explained the phase-in
schedule for certain other drugs. 71 Fed. Reg. 3,922, 3,965. The requirements for “older”
drugs and “newer” drugs, however, shared similar language. See Tucker v. SmithKline
Beecham Corp., 596 F. Supp. 2d 1225, 1228–30 (S.D. Ind. 2008) (comparing 21 C.F.R. §
201.80(e) with 21 C.F.R. § 201.57(c)(6)(i) and 21 C.F.R. § 201.57(e) (2002)).
16 In re Fosamax (Alendronate Sodium) Prods. Liab. Litig., 118 F.4th 322, 329 (3rd
Cir. 2024) (citing 21 C.F.R. § 201.57).
17 Albrecht, 587 U.S. at 304.
18 Id. (quoting Final Rule, Supplemental Applications Proposing Labeling Changes for
Approved Drugs, Biologics, and Medical Devices, 73 Fed. Reg. 49,603, 49,605–06 (Aug. 22,
2008)).
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a drug manufacturer ‘must describe clinically significant adverse reactions[,]
including any that are potentially fatal, are serious even if infrequent, or can
be prevented or mitigated through appropriate use of the drug[.]’”19 “That
section ‘must 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,’” but “‘a causal relationship need not have been definitely established’
before making such a revision.”20
“In the Adverse Reactions section of a label, the drug manufacturer must
‘describe the overall adverse reaction profile of the drug.’”21 An “‘adverse
reaction’ is ‘an undesirable effect, reasonably associated with use of a drug,
that may occur as part of the pharmacological action of the drug or may be
unpredictable in its occurrence.’”22 But “this definition does not include all
adverse events observed during use of a drug, only those adverse events for
which there is some basis to believe there is a causal relationship between the
drug and the occurrence of the adverse event.”23
As the Third Circuit has explained, “[t]o summarize, risks described in
the 	Warnings 	and 	Precautions 	section 	of 	a 	label 	(i.e., 	risks 	of 	clinically
significant adverse reactions) are presumably more serious than those that
appear only in the Adverse Reactions section.”24
19 In re Fosamax, 118 F.4th at 329 (quoting 21 C.F.R. § 201.57(c)(6)(i)) (alterations in
original).
20 Id. (quoting 21 C.F.R. § 201.57(c)(6)(i)) (citation modified).
21 Id. (quoting § 201.57(c)(7)).
22 Id. (quoting § 201.57(c)(7)).
23 § 201.57(c)(7) (emphasis added).
24 In re Fosamax, 118 F.4th at 329.
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B. 	Changes-Being-Effected regulation
“When the FDA approves a new drug, it also approves the exact text that
will be included on the drug’s labeling.”25 But “[a]fter the FDA approves a label
for a drug, that label is not immutable.”26 Because “knowledge about a drug’s
safety and efficacy can change over time,” the FDA provides several pathways
for a label change.27 Generally, a manufacturer cannot change a drug’s label
after approval until the FDA approves a supplemental application.28 “But in
some circumstances, the changes-being-effected (“CBE”) regulation allows
manufacturers 	to 	file 	a 	supplemental 	application 	with 	the 	FDA 	and
simultaneously 	implement 	a 	labeling 	change 	before 	obtaining 	FDA
approval.”29 	The 	FDA, 	however, 	may 	still 	reject 	labeling 	changes 	made
pursuant to the CBE regulation in its review of the supplemental application.30
Pursuant to 21 C.F.R. § 314.70(c)(6)(iii), a CBE change can be invoked
for “[c]hanges in the labeling to reflect newly acquired information . . . to
accomplish 	any 	of 	the 	following,” 	including 	“to 	add 	or 	strengthen 	a
contraindication, 	warning, 	precaution, 	or 	adverse 	reaction 	for 	which 	the
25 Hickey, 102 F.4th at 750 (citing Wyeth, 555 U.S. at 568).
26 In re Zofran (Ondansetron) Prods. Liab. Litig., 57 F.4th 327, 331 (1st Cir. 2023).
27 Id.
28 Hickey, 102 F.4th at 750 (citing Wyeth, 555 U.S. at 568).
29 Id. (citing 21 C.F.R. § 314.70(c)(6)).
30 Wyeth, 555 U.S. at 571. “If the FDA later disapproves the CBE application, ‘it may
order the manufacturer to cease distribution of the drug product(s)’ with the new labeling.”
Albrecht, 587 U.S. at 321 (Thomas, J., concurring) (alterations in original) (quoting 21 C.F.R.
§ 314.70 (c)(7)). But “in practice, manufacturers typically consult with FDA prior to adding
risk information to labeling.” In re Fosamax, 118 F.4th at 330 (quoting 71 Fed. Reg. 3,922,
3934 (Jan. 24, 2006)).
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evidence of a causal association satisfies the standard for inclusion in the
labeling under § 201.57(c) of this chapter.”31
Thus, the current CBE regulation allows a manufacturer to change a
label 	to 	reflect 	(1) 	“newly 	acquired 	information” 	if 	the 	changes 	add 	or
strengthen a warning for which there is (2) evidence of a causal association.32
21 C.F.R. § 314.3(b) defines “newly acquired information” as “data,
analyses, 	or 	other 	information 	not 	previously 	submitted 	to 	the 	Agency,”
including but not limited to “data derived from new clinical studies, reports of
adverse events, or new analyses of previously submitted data (e.g., meta-
analyses) if the studies, events or analyses reveal risks of a different type or
greater 	severity 	or 	frequency 	than 	previously 	included 	in 	submissions 	to
FDA.”33
In turn, as stated above, while the Warnings and Precautions section
requires “‘reasonable evidence of a causal association with a drug’ before a risk
will be listed,” the Adverse Reactions section requires only “some basis to
believe there is a causal relationship between the drug and the occurrence of
an adverse event.”34
III. 	Approval History
Sanofi submitted the original Taxotere NDA on July 24, 1994.35 On May
14, 1996, the FDA approved the Taxotere NDA for the treatment of patients
31 21 C.F.R. § 314.70(c)(6)(iii)(A).
32 See id.
33 (emphasis added).
34 In re Fosamax, 118 F.4th at 329 (first quoting 21 C.F.R. 201.57(c)(6)(i); then quoting
21 C.F.R. § 201.57(c)(7)).
35 Dr. Ross explains that Rhône-Poulenc Rorer (now Sanofi) submitted the original
NDA, which first received FDA approval in 1996 under the Accelerated Approval regulations
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with locally advanced or metastatic breast cancer whose disease progressed
during anthracycline-based therapy, or whose disease has relapsed during
anthracycline-based 	adjuvant 	therapy. 	The 	FDA 	subsequently 	approved
Taxotere for additional indications, including as an adjuvant chemotherapy
treatment for early-stage breast cancer in 2004.36 All FDA-approved dosing
indications for Taxotere involve infusions every three weeks. Although there
are no FDA-approved indications involving weekly infusions of Taxotere, it is
often prescribed off-label for such use.
Patients 	are 	treated 	with 	docetaxel 	in 	both 	the 	metastatic 	and
adjuvant/neoadjuvant setting. Metastatic disease, or Stage IV cancer that is
no longer curable, refers to cancer that has spread from its original site to other
parts of the body. Chemotherapy administered in this setting is given to
prevent cancer from spreading, that is, to prolong survival.37
By contrast, adjuvant chemotherapy is given as a supplement to the
primary 	treatment—typically 	surgery—for 	the 	purpose 	of 	preventing 	the
cancer from returning. Adjuvant chemotherapy is given after surgery, while
neoadjuvant therapy is given before surgery for the purpose of shrinking a
tumor before it is removed. Consequently, patients who receive docetaxel in
the metastatic setting receive it for much longer periods of time than patients
who are treated in the adjuvant/neoadjuvant setting.38
(21 C.F.R. §§ 314.500–.560). These regulations “allow provisional approval on the basis of an
effect on a clinical endpoint other than survival or irreversible morbidity. Accelerated
approval requires that the sponsor submit post-marketing data to describe and verify the
benefit of the drug.” Doc. 445-24 at 49.
36 Hickey, 102 F.4th at 751–52; see also Doc. 445-4 at 36, Doc. 485-11 at 1.
37 Doc. 445-27 at 13, 17 n.57.
38 Id.
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A. 	Correspondence with and submissions to the EMA
The parties provide evidence regarding Sanofi’s correspondence with the
European 	Agency 	for 	the 	Evaluation 	of 	Medicinal 	Products 	(“EMA”) 	for
background. 	In 	mid-2000, 	Sanofi 	received 	“a 	cluster” 	of 	nine 	“cases 	of
canalicular fibrosis and lacrimation disorders, which were reported from a
single non-[Sanofi] sponsored clinical trial” involving another drug, Herceptin,
and docetaxel.39 Afterwards, at the request of the EMA, Sanofi’s Global Safety
Officer for Taxotere prepared a cumulative review to “identify additional cases
of canalicular fibrosis, blocked tear ducts, lacrimal stenosis, and excessive
tearing.”40 The assessment was submitted to the EMA in the Eighth Periodic
Safety Update Report for Taxotere (“PSUR 8”) on February 1, 2001 and covered
the period between February 1 and November 3, 2000.41
Sanofi reported in 	PSUR 	8 that the 	nine patients from the 	study
described 	above 	“experienced 	tearing 	(epiphora) 	diagnosed 	as 	canalicular
fibrosis” (scarring), and that five of those patients required some form of
surgery.42 Sanofi also briefly summarized ten cases from spontaneous reports
“without 	significant 	confounding 	factors 	and 	requiring 	procedural
intervention.”43 seven cases of “excessive tearing,” one case of “blocked tear
39 Doc. 445-5 at 26.
40 Id.
41 Id.
42 Id. at 29. Based on the case numbers listed in PSUR 8, it is unclear whether nine
or ten patients were reported from this study. See id; see also Doc. 445-6 at 9 (noting that “10
cases of canalicular fibrosis were reported in the Phase II study of docetaxel plus
trastuzumab”).
43 A “spontaneous report” is an adverse event reported once the drug is marketed
which is unsolicited and which does not derive from a study or organized data collection
scheme. 445-5 at 101.
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ducts,” one of “lacrimal stenosis,” and one case of “canaliculitis” (inflammation
and infection of the canaliculi).44 Sanofi concluded that “[t]o date, there is no
clear mechanism of action for docetaxel to cause canalicular fibrosis.45
After Sanofi submitted PSUR 8 to the EMA, the EMA directed Sanofi to
submit the requisite documentation to add “lacrimal duct obstruction” to the
European 	label 	within 	two 	months.46 	In 	response, 	Sanofi 	compiled 	an
additional assessment, which was later integrated into the Ninth Periodic
Safety Update Report for Taxotere (“PSUR 9”) and submitted to EMA on
November 20, 2001.47
Sanofi stated in PSUR 9 that ten cases of lacrimal duct/canaliculi
stenosis were reported during the relevant period. Six of these cases were
44 According to the American Academy of Ophthalmology Eye Wiki, canaliculitis is “an
infection of the lacrimal canaliculus.” American Academy of Ophthalmology Eye Wiki,
https://eyewiki.org/Canaliculitis. (last visited Oct. 29, 2025). Dr. Esmaeli opines that
“canaliculitis, 	or 	inflammation 	and 	chronic 	infection 	of 	the 	canaliculi,” 	can 	cause
“stenosis/obstruction.” Doc. 445-27 at 11–12.
45 445-5 at 29 (emphasis added). In total, PSUR 8 referenced seventy cases from
CIOMS Forms, which “provide a standardized format for sponsors to report suspected
adverse drug reactions to regulatory authorities.” Doc. 445-4 at 40. Nine of the seventy cases
were reported from “intensified monitoring,” and sixty-one were reported from from
“spontaneous reports.” Id. Forty-six of the sixty-one spontaneous reports were considered
associated with docetaxel. 445-5 at 27. Only the cases described above were discussed in
detail for various reasons. Id. at 26–27.
46 Doc. 445-6 at 2. Specifically, the EMA instructed Sanofi to “provide a Type II
variation” to add “lacrimal duct obstruction” to the SmPC, or “Summary of Product
Characteristics,” which Sanofi’s proposed regulatory expert, Dr. Joohee Sul, explains “is
EMA’s functional equivalent to the USPI.” Doc. 445-4 at 43. A Type II variation is a “major
change to a marketing authorisation that may have a significant impact on the quality, safety
or efficacy of a medicine, but does not involve a change to the active substance, its strength
or the route of administration. Type II variations require a formal approval.” European
Medicines 	Agency, 	Type 	II 	Variation, 	G LOSSARY 	– 	REGULATORY 	TERMS,
https://www.ema.europa.eu/en/glossary-terms/type-ii-variation (last visited Oct. 29, 2025).
47 Doc. 527-9. The assessment was circulated to Sanofi’s labeling group as a “Request
for Global Labeling Discussion.” Doc. 445-8.
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reported from two publications, while four cases were from “spontaneous
reports.”48 The first publication was an abstract titled “Early Recognition of
Taxane-Associated 	Canaliculitis 	Important 	in 	Preserving 	Lacrimal 	Duct
Function,” which was published in 2000 by R. Kneuper Hall and others in
Breast Cancer Research and Treatment (“2000 Kneuper Hall Abstract”).49 The
second, “Canalicular Stenosis Secondary to Docetaxel (Taxotere): A Newly
Recognized Side Effect,” was published in 2001 in Ophthalmology by Dr. Bita
Esmaeli and others (“2001 Esmaeli Ophthalmology Article”).50 The parties
focus their arguments on these two publications.
Sanofi noted that in the articles, the authors suggested that docetaxel
may play a role either through (1) direct secretion into tears, potentially
causing fibrosis (scar tissue formation) in the canaliculi, which could lead to
cicatricial ectropion (outward turning of the eyelid due to scarring) and/or
dacryostenosis; 	or 	(2) 	through 	systemic 	effects 	of 	the 	drug 	similar 	to
generalized edema (swelling/fluid retention).51
In the cumulative review section, PSUR 9 also briefly summarized the
characteristics of thirty-five cases, including the ten described above, involving
“lacrimation disorder requiring intervention, tear duct obstruction, stenosis, or
canaliculitis,” and noted that ophthalmological findings were reported for nine
48 Doc. 445-9 at 21.
49 Kneuper Hall R. et al., Early Recognition of Taxane-Associated Canaliculitis
Important in Preserving Lacrimal Duct Function, 64 BREAST CANCER RES. TREAT. 89,
abstract 356 (2000).
50 	Bita Esmaeli et al., Canalicular Stenosis Secondary to Docetaxel (Taxotere): A
Newly Recognized Side Effect, O PHTHALMOLOGY (2001).
51 Doc. 445-9 at 66. Neither the parties nor their experts provide or otherwise point to
a definition for the term “dacryostenosis.”
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of these cases.52 Sanofi further stated that “although various terms referring
to the tear duct system were reported,” twenty-three cases reported having
undergone various procedures, including “stents/ tubes/ silicone intubation,”
“punctoplasty/ dilatation,” “temporary punctal plugs,” and “tear duct surgery
not otherwise specified” for the relief of symptomatic epiphora.53 Sanofi also
noted that topical ocular medications and fluorouracil (another chemotherapy
agent taken by some patients) had been described as being associated with
tearing.
Finally, Sanofi estimated that, based on crude estimates of patient
exposure data, the rate of cases reporting “tearing abnormality requiring
intervention,” as well as those possibly involving tear duct obstruction or
blockage, were at rates less than or equal to 1/10,000 patients or .01%.54 Sanofi
also noted that “patient exposure data is not available 	based on dosing
schedule.”55
B. 	Correspondence with and submissions to the FDA
1. 	15-Day ADE Report
As part of its post-marketing obligations, Sanofi submitted a 15-day
Adverse Drug Experiences (“ADE”) Report to the FDA in June 2001.56 The
52 Doc. 445-9 at 66. PSUR 9 also identified 147 cases of tearing abnormalities from
Sanofi’s database as of August 17, 2001. Doc. 445-9 at 65.
53 Id. at 65.
54 Id. Sanofi presented similar estimates in PSUR 8. Doc. 445-5 at 29.
55 Doc. 445-9 at 66.
56 Pursuant to 21 C.F.R. § 314.80(c), an applicant must submit Postmarketing 15–day
“Alert reports,” or reports on “each adverse drug experience that is both serious and
unexpected, whether foreign or domestic, as soon as possible but no later than 15 calendar
days from initial receipt of the information by the applicant,” as well as “Periodic adverse
drug experience reports.”
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Report 	contained 	MedWatch forms 	describing 	patients 	requiring 	surgical
intervention described in the 2000 Kneuper Hall Abstract and the 2001
Esmaeli Ophthalmology Article.57
The 2000 Kneuper Hall Abstract reported on six patients who were
treated 	with 	docetaxel 	and/or 	docetaxel 	and 	paclitaxel 	who 	experienced
canaliculitis “symptomatically manifested as epiphora.”58 Of the six patients,
three 	required 	“lacrimal 	duct 	stents”—two 	patients 	required 	“temporary
silicone 	punctal 	plugs” 	and 	one 	patient 	required 	bilateral
dacryocystorhinostomy 	with 	insertion 	of 	permanent 	Jones 	tubes.59 	The
authors concluded that “[w]ith the increased use of taxanes it is important that
medical oncologists be cognizant of this ocular toxicity which may lead to
lacrimal canalicular fibrosis with permanent stenosis.”60
In turn, the 2001 Esmaeli Ophthalmology Article was an observational
study of three metastatic breast cancer patients who received weekly docetaxel
and/or docetaxel and trastuzumab and who developed epiphora “secondary to
punctal or canalicular stenosis during treatment with docetaxel.”61 Epiphora
did not resolve after cessation of treatment in two of the three patients. One
57 Doc. 445-10. Dr. Sul states in her Report that “FDA maintains MedWatch, a publicly
available web-based reporting system for adverse events related to products regulated by
FDA, including prescription drugs.” Doc. 445-4 at 28.
58 Doc. 445-10 at 23. Four patients treated adjuvantly received docetaxel every three
weeks, and two patients with metastatic disease received docetaxel weekly followed by
paclitaxel. Id.
59 While the authors appear to refer to the treatment as both “stents” and “punctal
plugs,” the authors apparently intended to refer to stents. Dr Esmaeli distinguishes punctal
plugs (used to treat dry eye) from stents and opines that “[p]atients with a history of having
punctal plugs likely have a prior history of dry eye and tearing,” and opines that “[p]unctal
plugs can cause stenosis/obstruction.” Doc. 445-27 at 7, 12.
60 Doc. 445-10 at 23.
61 Id. at 22. The patients also received dexamethasone coverage.
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patient underwent snip punctoplasty with partial resolution of her symptoms,
one patient underwent bicanalicular silicone intubation of each nasolacrimal
duct with resolution of her symptoms, and one patient opted out of suggested
procedures.
The authors stated that while “[c]analicular stenosis has been described
in association with other chemotherapeutic agents . . . to our knowledge, it has
not been reported as a side effect of docetaxel.”62 The authors concluded that
[e]piphora is a newly recognized side effect of docetaxel and may
occur 	more 	frequently 	with 	weekly 	cycles 	of 	this 	drug. 	The
mechanism for epiphora seems to be punctal and canalicular
stenosis. This side effect, in advanced cases, is not reversible with
discontinuation of the drug. Patients being administered weekly
cycles of docetaxel should be screened for epiphora and canalicular
stenosis, 	and 	treatment 	in 	the 	form 	of 	silicone 	intubation 	or
punctoplasty should be considered in early stages to prevent the
need for conjunctivodacryocystorhinostomy.63
2. 	2002 CBE submission
Pursuant to the CBE regulations, on January 9, 2002, Sanofi submitted
a “Special Supplement-Changes Being Effected” to the FDA for Taxotere
(“Supplement 17”). Supplement 17 included changes to the Adverse Reactions
section of the Taxotere label to be implemented no later than May 31, 2002.
Specifically, Sanofi proposed adding a new “Ophthalmologic” subsection to the
Adverse Reactions section and provided the following rationale:
The subsection Ophthalmologic has been added and contained
the following events: conjunctivitis, lacrimation or lacrimation
with or without conjunctivitis (line listings for these events are
62 Id.
63 Id. (emphasis added).
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contained in Attachments 10 and 11). Based on our medical review
. . . the event lacrimal duct obstruction has been classified as
“rare.” 	The 	addition 	of 	this 	event 	has 	been 	described 	in 	the
following 	statement: 	“Rare 	cases 	of 	lacrimal 	duct 	obstruction
resulting in excessive tearing have been reported primarily in
patients receiving other anti-tumor agents concomitantly” (line
listings for this event is contained in Attachment 12).64
Supplement 	17 	also 	included 	fifty-three 	case 	line 	listings 	for 	the 	event
“lacrimal duct obstruction.” The listings identified various terms including
“lacrimal 	duct 	obstruction,” 	“canaliculitis,” 	“clogged 	tear 	ducts,” 	and
“canalicular stenosis.”65
On March 27, 2002, the FDA responded to Sanofi’s CBE application and
sent a “request for changes,” and countered with the following language:
Cases of lacrimal duct obstruction resulting in excessive tearing
and/or 	requiring silastic tube replacement 	have been reported
primarily 	in 	patients 	receiving 	other 	anti-tumor 	agents
concomitantly.66
Following the FDA’s response, Sanofi held further discussions regarding
the FDA’s addition of the silastic tubing language and internally circulated
various draft responses to the FDA via email. In one email, a Sanofi employee
objected to the inclusion of the “silastic tubing” language on the label, stating
that “not patient ‘requires’ silastic tubing; it is merely an intervention of
convenience.”67 In one draft, a Sanofi employee proposed responding to the
64 Doc. 445-12 at 6–7. Sanofi classified the event as rare because there were fewer than
309 events, and advised that the events in postmarketing experiences should be described as
“reported from a population of unknown size, so precise estimates of frequency could not be
made.” Doc. 493-24 at 5.
65 Doc. 445-12, Doc. 445-13.
66 Doc. 445-15 at 2 (emphasis added).
67 Doc. 493-29 at 2.
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FDA by stating that “[r]eview of the literature indicated that all fourteen
patients were treated by a single ophthalmologist, outside of the context of a
controlled clinical trial,” and that “[t]he risk-benefit ratio for this procedure, in
this clinical setting, has not been defined, and thus we respectfully request
that it would not be appropriate at this time to include a specific medical
procedure in the labeling.”68 In another draft, an employee questioned whether
silastic tubing was a “widely accepted intervention.”69
On May 28, 2002, Sanofi responded to the FDA with the following
proposed language:
Excessive tearing which may be attributable to lacrimal duct
obstruction has been reported primarily in patients receiving other
anti-tumor agents concomitantly.70
In its response, Sanofi noted that many of the patients managed with silastic
tubes were treated at the same medical center and that some patients required
other interventions (such as DCR, punctoplasty, etc.). Thus, Sanofi explained
that it removed the silastic tubing language because it was “inappropriate” to
recommend “a specific medical intervention,” and stated that the “specific
treatment modality” should be based on the treating physician’s assessment
and “the current standard of care for the management of this condition in the
medical community.”71
68 Doc. 527 at 24.
69 Id. at 25.
70 Doc. 445-18.
71 Id.
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On 	May 	29, 	2002, 	the 	FDA 	countered 	Sanofi’s 	language 	with 	the
following, noting that excessive tearing had also been reported in patients
receiving docetaxel alone:
Excessive tearing which may be attributable to lacrimal duct
obstruction has been reported.72
On June 5, 2002, Sanofi notified the FDA that it agreed to this proposal.
On July 9, 2002, the FDA notified Sanofi that it had approved Supplement 17.
3. 	sNDA submission
Around 	this 	time, 	on 	February 	1, 	2002, 	Sanofi 	also 	submitted 	a
Supplemental 	NDA 	(sNDA) 	seeking 	approval 	for 	the 	use 	of 	Taxotere 	in
combination with “cisplatin for treatment of patients with unresectable, locally
advanced 	or 	metastatic 	non-small 	cell 	lung 	cancer,” 	and 	“who 	have 	not
previously 	received 	chemotherapy 	for 	this 	condition.”73 	As 	part 	of 	this
application, Sanofi submitted PSURs 8 and 9 to the FDA.74 Taxotere was
approved for this indication on November 27, 2002.75
C. 	Subsequent label revisions
From September 2002 until 2003, the warning on the label provided:
72 Doc. 445-19.
73 Doc. 445-14 at 2.
74 In their Opposition, Plaintiffs dispute that Sanofi has proven that it submitted the
documents to the FDA. The sNDA states that “[t]o represent the collective post-marketing
experience of docetaxel, an overview assessment is presented with a copy of the Periodic
Safety Update Reports (PSURs) compiled according to ICH E2 recommendations.” Doc. 445-
14 at 4. Sanofi attached to its Reply “[t]he file location data for the PSUR attachment with
the NSCLC submission.” Doc. 525 at 13 n.31.
75 Doc. 527 at 4–5.
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Ophthalmologic: conjunctivitis, lacrimation or lacrimation with or
without 	conjunctivitis. 	Excessive 	tearing 	which 	may 	be
attributable to lacrimal duct obstruction has been reported.76
In 2003, Sanofi again revised the label to state:
Ophthalmologic: conjunctivitis, lacrimation or lacrimation with or
without 	conjunctivitis. 	Excessive 	tearing 	which 	may 	be
attributable to lacrimal duct obstruction has been reported. Rare
cases of transient visual disturbances (flashes, flashing lights,
scotomata) 	typically 	occurring 	during 	drug 	infusion 	and 	in
association with hypersensitivity reactions have been reported.
These were reversible upon discontinuation of the infusion.77
This language remained largely the same until the label was revised in May
2020 to change the “reversible upon discontinuation” language.78 Since May
2020, the label has contained the following warning:
Ophthalmologic: conjunctivitis, lacrimation or lacrimation with or
without conjunctivitis, cystoid macular edema (CME). Excessive
tearing which may be attributable to lacrimal duct obstruction.
Transient visual disturbances (flashes, flashing lights, scotomata),
typically 	occurring 	during 	drug 	infusion 	and 	reversible 	upon
76 Doc. 493-43.
77 Doc. 493-44 (emphasis added).
78 Doc. 493-64. In December 2013, the label was revised to include as the final sentence
that “[c]ases of cystoid macular edema (CME) have been reported in patients treated with
TAXOTERE.” Doc. 493-58.
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discontinuation 	of 	the 	infusion, 	in 	association 	with
hypersensitivity reactions.79
LEGAL STANDARD
On February 28, 2025, Sanofi filed the instant Motion for Summary
Judgment based on Preemption.80 Plaintiffs oppose.81
I. 	Summary Judgment
Summary 	judgment 	is 	appropriate 	“if 	the 	pleadings, 	depositions,
answers to interrogatories, and admissions on file, together with affidavits, if
any, show that there is no genuine issue as to any material fact and that the
moving party is entitled to a judgment as a matter of law.”82
II. 	Law on Preemption
The 	doctrine 	of 	preemption 	derives 	from 	the 	U.S. 	Constitution’s
Supremacy Clause, which provides that “federal law ‘shall be the supreme Law
of the Land . . . any Thing in the Constitution or Laws of any State to the
Contrary notwithstanding.’”83 “Where state and federal law ‘directly conflict,’
state law must give way.”84 Such a conflict exists “where it is ‘impossible for a
private 	party 	to 	comply 	with 	both 	state 	and 	federal 	requirements.’”85
“Impossibility preemption is a demanding defense.”86
79 Doc. 527 at 29.
80 Doc. 445.
81 Doc. 485.
82 Sherman v. Hallbauer, 455 F.2d 1236, 1241 (5th Cir. 1972).
83 PLIVA v. Mensing, 564 U.S. 604, 617 (2011) (quoting U.S. CONST. art. VI, cl. 2)
(alterations in original).
84 Id. (quoting Wyeth, 555 U.S. at 583).
85 Id. at 618 (quoting Freightliner Corp. v. Myrick, 514 U.S. 280, 287 (1995)).
86 Wyeth, 555 U.S. at 573.
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A preemption analysis must be guided by the two cornerstones 	of
preemption jurisprudence.87 First, a court should consider “the purpose of
Congress.”88 Second, in all preemption cases, a court must assume “that the
historic police powers of the States were not to be superseded by the Federal
Act unless that was the clear and manifest purpose of Congress.”89
As the Supreme Court has explained, “the underlying question . . . is
whether federal law (including appropriate FDA actions) prohibited the drug
manufacturer from adding any and all warnings to the drug label that would
satisfy state law.”90 “The question for ‘impossibility’ is whether the private
party could independently do under federal law what state law requires of it.”91
“A state law challenge to FDA-approved warnings, including a tort action
under state law, can thus proceed only when the defendant had the unilateral
ability to change that labeling; otherwise, the claim is preempted.”92
As explained above, the CBE regulation allows a unilateral label change
where there is (1) newly acquired information for which there is (2) evidence of
a causal association between the drug and the harm. In Hickey v. Hospira, the
Fifth Circuit established that in this preemption context, “the availability of
the CBE regulation is a threshold issue” to the preemption analysis.93 Thus, if
87 Id. at 565.
88 Id.
89 Id.
90 Knight v. Boehringer, 984 F.3d 329, 337 (4th Cir. 2021) (emphasis added) (quoting
Albrecht, 587 U.S. at 313–314).
91 Mensing, 564 U.S. at 604 (citing Wyeth, 555 U.S. at 573).
92 Knight, 984 F.3d at 337.
93 Hickey, 102 F.4th at 754.
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the requirements of the CBE regulation are not satisfied, a plaintiff’s claims
are preempted.
If the CBE regulation is available, a plaintiff’s claims are nevertheless
preempted if a manufacturer can show “‘clear evidence that the FDA would not
have approved a change’ to the label.”94 In Merck Sharp & Dohme Corp. v.
Albrecht, the Supreme Court clarified that “clear evidence” is “evidence that
shows the court that the drug manufacturer fully informed the FDA of the
justifications for the warning required by state law and that the FDA, in turn,
informed the drug manufacturer that the FDA would not approve a change to
the drug’s label to include that warning.”95
To reiterate, in a case such as this one, the preemption inquiry is a two-
part test. First, a court must determine if the CBE regulation (which allows
for a unilateral change to the label) was available by assessing whether the
requirements set forth in the regulation are satisfied. If so, a defendant can
still prove impossibility preemption by showing there was “clear evidence” that
the FDA would have rejected a label change.
LAW AND ANALYSIS
Sanofi 	argues 	that 	Plaintiffs’ 	state-law 	failure-to-warn 	claims 	are
preempted by the FDCA and its corresponding regulations because it could not
have invoked the CBE regulation to unilaterally change its label. Because
Sanofi moves only on this threshold issue, it does not address the “clear
evidence” standard. As explained above, the CBE regulation allowing for a
94 Albrecht, 587 U.S. at 300 (quoting Wyeth, 555 U.S. at 571).
95 Id. at 303.
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change 	to “add 	or 	strengthen 	a warning” requires 	both “newly acquired
information” and sufficient evidence of a causal association between the drug
and a risk of harm.96 Here, however, Sanofi argues only that it did not have
“newly acquired information” as defined in the regulation.
Plaintiffs first respond that the CBE regulation was amended in 2008 to
include the requirement of “newly acquired information.” As such, “newly
acquired information” was not required before then, and Sanofi could have
used 	the 	CBE 	process 	to 	strengthen 	the 	warning 	even 	without 	such
information. They further contend that, even if the regulation did require
“newly acquired information,” Sanofi had it as early as 2003, citing several
scientific publications.
I. 	Burden of Proof
At the outset, the parties disagree about who bears the burden of proof
regarding the availability of the CBE regulation. “The burden of establishing
the nonexistence of a ‘genuine issue’ is on the party moving for summary
judgment.”97 “This burden has two distinct components: an initial burden of
production, which shifts to the nonmoving party if satisfied by the moving
party; and an ultimate burden of persuasion, which always remains on the
moving party.”98 “The burden of production imposed by Rule 56 requires the
moving party to make a prima facie showing that it is entitled to summary
judgment.”99
96 While the CBE change allows for certain additional categories of label changes, the
parties do not address those here.
97 Celotex Corp. v. Catrett, 477 U.S. 317, 323 (1986) (Brennan, J., dissenting) (citing
10A Wright & Miller’s FEDERAL PRACTICE & PROCEDURE § 2727 (2d ed. 1983)).
98 Id. (citing 10A Wright & Miller § 2727).
99 Id. (citing 10A Wright & Miller § 2727).
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In this preemption context, district courts, including this Court, have
held that the manufacturer bears “the ultimate burden of persuasion,” but the
plaintiff “bears an initial burden of production.”100 This allocation reflects the
unique posture of preemption as an affirmative defense: defendants must
ultimately establish the absence of “newly acquired information” that would
have permitted a unilateral labeling change, yet plaintiffs may bear a limited
burden of production to identify evidence suggesting such information exists,
so as not to require defendants to prove a negative.101 Here, while Defendants
agree with this approach, Plaintiffs assert that Defendants bear the full
burden, including the burden of production.
In Hickey v. Hospira, Inc., the Fifth Circuit held that “Defendants bear
the ultimate burden of proving that the information at issue does not meet the
requirements 	of 	the 	CBE 	regulation.”102 	The 	court 	noted, 	however, 	that
because the parties agreed that the defendants bear this burden, and because
the plaintiffs had “already identified the information at issue,” it “need not
decide which party bears the initial burden of producing the information at
issue.”103
100 See Silverstein v. Boehringer Ingelheim Pharms., Inc., No. 19-CIV-81188, 2020 WL
6110909, at *12 (S.D. Fla. Oct. 7, 2020). In another MDL, this Court adopted the approach
set forth in Silverstein; however, on appeal, the Fifth Circuit declined to decide the issue. In
re Taxotere (Docetaxel) Prods. Liab. Litig., MDL No. 16-2740, 16-17583, 18-194, 17-12674,
18-9799, 18-4731, 2022 WL 3042639, at *8 (E.D. La. Aug. 2, 2022), vacated and remanded on
other grounds sub nom., Hickey, 102 F.4th 748.
101 See Silverstein, 2020 WL 6110909, at *12.
102 Hickey, 102 F.4th at 755. To the extent the question is a legal one, “the burden of
proof is not a determining factor.” Roberto, 2019 WL 5068452, at *11 n.9. “Standards of proof,
such as preponderance of the evidence and clear and convincing evidence, have no place in
the resolution of this question of law.” Albrecht, 587 U.S. at 325 (Alito, J., concurring).
103 Hickey, 102 F.4th at 761.
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Here too, the Court finds that it need not decide the issue because
Plaintiffs have already identified the relevant information.
II. 	Whether “Newly Acquired Information” Is a Question for Jury
Determination
The parties also appear to dispute whether the existence of “newly
acquired information” is a question for a judge or a jury to determine.104 In
Albrecht, 	the 	Supreme 	Court—addressing 	only 	Wyeth 	v. 	Levine’s 	“clear
evidence” standard—held that the question of agency disapproval in the
evaluation of “clear evidence” is a question of law that a judge must decide.105
The Court pronounced that “the fact/law distinction at times has turned on a
determination that, as a matter of the sound administration of justice, one
judicial 	actor 	is 	better 	positioned 	than 	another 	to 	decide 	the 	issue 	in
question.”106 The Court explained that judges are “better suited than are juries
to understand and to interpret agency decisions in light of the governing
statutory and regulatory context,” and that even when “contested brute facts”
are relevant, they are “subsumed within an already tightly circumscribed legal
analysis.”107 It also made clear that “‘courts may have to resolve subsidiary
factual disputes’ that are part and parcel of the broader legal question.”108
For example, “in contexts as diverse as the proper construction of patent
claims and the voluntariness of criminal confessions,” such factual inquiries
104 Sanofi also raises this issue in its Motion to Exclude Dr. Ross, arguing that his
opinions on “newly acquired information” are legal conclusions. Doc. 456.
105 In re Zofran, 57 F.4th at 337 n.7 (citing Albrecht, 587 U.S. at 316).
106 Albrecht, 587 U.S. at 318 (quoting Markman v. Westview Instruments, 517 U.S.
370, 388 (1996)).
107 Id. at 301.
108 Id. at 317 (quoting Teva Pharms. USA, Inc. v. Sandoz, 547 U.S. 318, 319 (2015)).
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“create a question that ‘falls somewhere between a pristine legal standard and
a simple historical fact.’”109 The Court explained that although at times such
quasi-factual inquiries may require credibility determinations, “any credibility
determinations will be subsumed within the necessarily sophisticated analysis
of the whole document, required by the standard construction rule that a term
can be defined only in a way that comports with the instrument as a whole.”110
The Court concluded that “courts should treat the critical question not
as a matter of fact for a jury but as a matter of law for the judge to decide. And
where that is so, the judge must simply ask himself or herself whether the
relevant 	federal 	and 	state 	laws 	‘irreconcilably 	conflic[t].’”111 	The 	Court,
however, “seemingly left open the question whether what constitutes ‘newly
acquired information’ is a question of law or a question of fact.”112
Following Albrecht’s reasoning, courts have confirmed that the question
of whether information is “newly acquired” is not one for expert testimony or
jury 	resolution. 	In 	Roberto 	v. 	Boehringer 	Ingelheim 	Pharms., 	Inc., 	the
Connecticut Superior Court reasoned that if the “clear evidence” prong is for
judges, “it seems unlikely that the Supreme Court would hold that the first
prong [newly acquired information] is triable to the jury while the second prong
is not.”113
109 Id. (quoting Markman, 517 U.S. at 388).
110 Id. In a concurring opinion, Justice Alito explained that “whether federal law
allowed Merck to include in the Fosamax label the warning alleged to be required by state
law is a question of law to be decided by the courts, not a question of fact.” Id. at 323 (Alito,
J., concurring).
111 Id. at 315 (quoting Rice v. Norma Williams Co., 458 U.S. 654, 659 (1982)).
112 In re Zofran, 57 F.4th at 337 n.7.
113 No. CPLHHDCV166068484S, 2019 WL 5068452, at *3 (Conn. Super. Ct. Apr. 2,
2020).
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Courts presiding over MDLs have precluded expert testimony on the
ultimate issue of whether something is “newly acquired.” For example, in In re
Zofran, the First Circuit, “[f]ollowing the parties’ lead,” proceeded “under the
assumption that determining whether certain information is ‘newly acquired’
is a legal question.”114 The court therefore found inadmissible the opinion of
the plaintiffs’ regulatory expert, Dr. Harvey, who opined that certain studies
constituted “newly acquired information.” The court explained that “[a]lthough
experts can opine on the underlying factual questions, including providing
interpretations of pharmaceutical studies, they provide little, if any, relevant
assistance 	when 	they 	opine 	on 	the 	ultimate 	legal 	question 	of 	whether
something 	is 	‘newly 	acquired 	information.’”115 	The 	court 	cited 	Knight 	v.
Boehringer, in which the Fourth Circuit held that “preemption is a question of
law 	that 	is 	reviewed 	de 	novo,” 	and 	further 	determined, 	“as 	part 	of 	its
preemption analysis, whether data was ‘newly acquired information.’”116
In In re Gardasil, the District Court for the Western District of North
Carolina, citing Zofran and Albrecht, also considered the admissibility the
testimony 	of 	a 	regulatory 	expert, 	Dr. 	Amato, 	on 	“newly 	acquired
information.”117 The court found that “[t]o the extent that Dr. Amato goes
beyond presenting evidence of the alleged ‘newly acquired information’ for the
Court to itself consider, he is offering his own interpretation as to whether the
data was sufficient to meet the governing standard.”118 The court thus barred
114 In re Zofran, 57 F.4th at 337.
115 Id. at 340.
116 Id. (citing Knight, 984 F.3d at 337).
117 3:22-MD-03036, 2025 WL 1782576, at *3 (W.D. N.C. Feb. 20, 2025) (quoting In re
Zofran, 57 F.4th at 340).
118 Id.
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Dr. Amato’s testimony “on the ultimate regulatory issue,” reasoning that it
went “to heart of what the Court must decide” because “opinions as to legal
conclusions cannot assist the Court in deciding questions which the Court must
answer as a matter of law.”119
The court considered, however, the expert’s testimony to the extent that
the expert was “providing factual information” and “describing the details and
timing 	of 	the 	warnings” 	that 	the 	plaintiffs 	contended 	should 	have 	been
included on the defendants’ label, finding that such testimony would “assist[]
the Court in making its ruling.”120
For the same reasons, the Court agrees that the question of whether
information is “newly acquired” is a question for a judge, rather than a jury, to
determine. And regardless of the precise nature of that question, to the extent
that any expert is opining on the “ultimate issue” of whether any scientific
literature satisfies the standard for “newly acquired information,” the Court
finds such testimony unhelpful and need not consider it.
III. 	Whether “Newly Acquired Information” was Required Prior to
2008
Prior to 2008, a CBE change could be made to “accomplish any of the
following,” 	including, 	among 	other 	things, 	“add 	or 	strengthen 	a
contraindication, warning, precaution, or adverse reaction.”121 The “newly
acquired” information requirement was codified in a 2008 Final Rule. 122 As
119 Id. at *3.
120 Id.
121 Doc. 493 at 3–4 (citing 21 C.F.R. § 314.70(c)(2)(i) (1985); 21 C.F.R. § 314.70(c)(6)(iii)
(effective September 22, 2008)).
122 73 Fed. Reg. 49,603 (2008).
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such, Plaintiffs contend that prior to 2008, “newly acquired information” was
not required for a CBE change. Defendants respond that the 2008 amendment
was not substantive, relying on the FDA’s statements in the preamble to the
2008 Final Rule, including its assertion that the amendments “codified the
Agency’s longstanding view” as to when a CBE change was appropriate.123
Here, as explained below, the Court finds that regardless of whether
“newly required information” was required to change a label under the CBE
regulation 	prior 	to 	2008, 	there 	exists 	on 	the 	record 	“newly 	acquired
information” such that Sanofi could have changed its label as early as 2003
even under the amended regulation.124
123 Id.
124 To be sure, where a statute or regulation lacks an explicit requirement, the Fifth
Circuit has cautioned against reading one in. Env’t Integrity Project v. EPA, 969 F.3d 529,
541 (5th Cir. 2020) (“‘The principle that a matter not covered is not covered is so obvious that
it seems absurd to recite it.’” (quoting Yates v. Collier, 868 F.3d 354, 369 (5th Cir. 2017))). “A
number of cases have identified the casus omissus pro omisso habendus est canon, under
which a statute should not be read to include matter it does not include.” Id. (citing Lamie v.
U.S. Tr., 540 U.S. 526, 538 (2004)). Because the regulation lacked the explicit definition of
“newly acquired information” currently in place, the FDA’s statements may not require
deference under Skidmore or Auer. See Huntington Ingalls, Inc. v. Dir., Off. of Worker’s
Comp. Programs, U.S. Dep’t of Labor, 70 F.4th 245, 254 (5th Cir. 2023) (first citing Skidmore
v. Swift & Co., 323 U.S. 134 (1944); then citing Auer v. Robbins, 519 U.S. 452 (1997)); but see
Gaetano v. Gilead Scis., Inc., 529 F. Supp. 3d 333, 348 n.10 (D.N.J. 2021) (concluding that
the “FDA effectively had the newly acquired information requirement in place prior to 2008,
even if it was not codified in the regulation”). Thus, prior to 2008, courts apparently did not
address the issue in determining whether the CBE process was available, although some
courts have suggested that there must at least be “reasonable” evidence supporting a label
change, as is required to list a warning. See In re Actos (Pioglitazone) Prods. Liab. Litig., No.
6:11-md-2299, 2014 WL 60298 (W.D. La. 2014); Cartwright v. Pfizer, Inc., 369 F. Supp. 2d
876, 886 (E.D. Tex. 2005); Tucker v. SmithKline Beecham Corp., 596 F. Supp. 2d 1225, 1230
(S.D. Ind. 2008); Bueno v. Merck & Co., 746 F. Supp. 3d 853, 876 (S.D. Cal. 2024). Although
Defendants point out that courts have also stated that the information at issue had to at least
be “new,” they also suggest that the definition of “newly acquired” is narrower than this. In
any event, whether information was “new,” or whether it had already been considered by the
FDA, seems less central to the pre-2008 inquiry into whether the CBE regulation was
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IV. 	Whether There Exists “Newly Acquired Information”
Plaintiffs argue that Sanofi had “newly acquired information” as early
as 2003 allowing it to strengthen the warning on the label.125 Specifically,
Plaintiffs point to a study by Dr. Bita Esmaeli and others titled “Blockage of
the Lacrimal Drainage Apparatus System as a Side Effect of Docetaxel”
published in Cancer (“2003 Esmaeli Cancer Study”).126 Plaintiffs also point to
additional pieces of literature published after this date that they contend
constitute “newly acquired information.”
available; rather, it appears to bear more directly on step two of the analysis—namely,
whether there was “clear evidence” that the FDA would have rejected a label change. See
Warner v. Amgen Inc., No. 1:24-cv-10632, 2025 WL 490720, at *7 (D. Mass. Feb. 13, 2025),
appealed docketed, 25-1268 (1st Cir. Nov. 20, 2025) (“Stated differently, when the FDA has
considered the safety and efficacy information required by state law in the course of
approving a prescription drug’s label, there exists clear evidence that the FDA would not
have approved the warning required by state law.”); see also Hickey, 102 F.4th at 759 n.8
(noting that the “line so drawn lets the FDA be the exclusive judge of safety and efficacy
based on information available at the commencement of marketing, while allowing the states
to reach contrary conclusions when new information not considered by the FDA develops”
(quoting In re Celexa & Lexapro Mktg. & Sales Pracs. Litig., 779 F.3d 34, 39 (1st Cir. 2015))).
125 As Sanofi points out, where a single plaintiff is involved in the litigation, or where
a defendant’s motion is tied to a specific plaintiff, the relevant time period to identify “newly
acquired information” runs from the time the FDA approved the relevant label available to
the plaintiff’s physician to the plaintiff’s exposure to the drug—although it is unclear whether
that time period should end at the time a plaintiff is first exposed, or the time a plaintiff has
finished treatment. See, e.g., Goodell v. Bayer Healthcare Pharms. Inc., No. 18-CV-10694-IT,
2019 WL 4771136, at *4 (D. Mass. Sept. 30, 2019) (limiting preemption inquiry to 2007, when
FDA approved most recent drug label, to 2010, when the plaintiff was administered the drug);
see also Rayes v. Novartis Pharms. Corp., No. 21-55723, 2022 WL 822195, at *1 (9th Cir. Mar.
18, 2022) (limiting “newly acquired information” to information published before the
plaintiff’s final injection of the drug at issue). In their Opposition, Plaintiffs point to the 2003
Esmaeli Cancer Study as the earliest publication constituting “newly acquired information.”
Doc. 485 at 18.
126 Esmaeli et al., Blockage of the Lacrimal Drainage Apparatus as a Side Effect of
Docetaxel Therapy, 98 CANCER 504 (2003) (Doc. 445-26).
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As stated above, “newly acquired information” is “data, analyses, or
other information not previously submitted to the Agency,” including but not
limited to “data derived from new clinical studies, reports of adverse events, or
new analyses of previously submitted data (e.g., meta-analyses) if the studies,
events or analyses reveal risks of a different type or greater severity or frequency
than previously included in submissions to FDA.”127 Thus, to assess whether
information satisfies the definition of 	“newly acquired,” 	the Court must
measure it against the information previously submitted to FDA. 128
Prior to 2003, Sanofi had submitted to the FDA (1) the 15-day ADE
Report, which included cases from the 2000 Kneuper Hall Abstract and 2001
Esmaeli 	Ophthalmology 	Article; 	(2) 	Supplement 	17, 	which 	included 	as
attachments 	case 	line 	listings; 	and 	(3) 	the 	February 	2002 	sNDA, 	which
included PSURs 8 and 9.129 Sanofi argues that these submissions already (1)
identified 	the 	risk 	of 	“permanent” 	stenosis, 	(2) 	indicated 	that 	surgical
procedures could be required, and (3) warned about the need for prompt
evaluation and referral. It therefore contends that the 2003 Esmaeli Cancer
Study provided nothing new upon which a CBE change could be based. The
Court disagrees.
In the 2003 Esmaeli Cancer Study, the authors evaluated the records of
148 patients with several types of cancer who had epiphora associated with
127 21 C.F.R. § 314.3(b) (emphasis added).
128 See Hickey, 102 F.4th at 757. In Hickey v. Hospira, the question before the court
was whether the plaintiffs’ claims against certain “505(b)(2) manufacturers” were preempted;
the court thus compared the publicly available “pre-approval” literature to the publicly
available “post-approval” literature. See id. at 756 n.5.
129 Although Dr. Sul contends in her report that Sanofi submitted other articles (in
2003 and afterwards) to the FDA, the parties do not mention those submissions.
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docetaxel.130 The purpose of the 2003 Study was “to report on the severity and
management of canalicular and nasolacrimal duct stenosis as a side effect of
docetaxel therapy and to report the outcome of surgical intervention for this
condition.”131
Two patients received treatment in the neoadjuvant setting, while the
remainder 	were 	treated 	in 	the 	metastatic 	setting. 	Seventy-one 	patients
received docetaxel weekly, 5 patients received docetaxel every two weeks, and
72 	patients 	received 	it 	every 	three 	weeks. 	Each 	patient 	underwent 	an
ophthalmologic examination and in-office probing and irrigation. The patients
were either treated with topical steroids or offered a surgical procedure,
depending on the severity of the stenosis.132
Thirty patients who received weekly docetaxel underwent surgery to
correct epiphora, including temporary silicone tube placement, DCR with
temporary silicone tube placement, and DCR with permanent Pyrex glass tube
placement. Twenty-nine of the 30 patients who underwent surgery reported
improvement or total resolution of epiphora after the procedure. In one patient,
the nasolacrimal duct and canaliculi scarred around the inserted silicone tube
after DCR and silicone intubation, so her symptoms persisted. Ten additional
patients who received weekly docetaxel had complete closure of their canaliculi
but elected not to undergo surgery. The authors noted that “[o]f special note
were two patients who received weekly docetaxel in the neoadjuvant setting
and developed complete closure of the canaliculi.”133
130 Doc. 445-26.
131 Id. at 2.
132 Id.
133 Id. at 4.
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Of the patients who received docetaxel every two or three weeks, only 3
patients required a surgical intervention to correct epiphora. One patient
underwent silicone intubation, 1 patient underwent DCR with silicone tube
placement, and 1 patient underwent punctoplasty.
The authors stated that “the findings in this large cohort confirm our
earlier observations that blockage of the lacrimal drainage apparatus is a
common and important side effect of weekly docetaxel therapy,” and that “this
ocular complication can occur even in the neoadjuvant setting when the drug
is used for a limited time, as evidenced by the finding of severe end-stage
canalicular stenosis in two individuals with breast carcinoma who received
adjuvant docetaxel.”134
The authors concluded that
[c]analicular and nasolacrimal duct obstruction is a common side
effect of weekly docetaxel therapy and can occur even when this
drug is used in the neoadjuvant setting. The results of the current
study 	indicate 	that 	early 	temporary 	silicone 	intubation 	in
symptomatic 	patients 	receiving 	weekly 	docetaxel 	can 	prevent
further closure of the lacrimal drainage apparatus and obviate
more involved surgical interventions and permanent Pyrex glass
tube placement. 135
Here, the Court finds that the 2003 Esmaeli Cancer Study shows a “risk
of a different type or greater severity or frequency” than what was previously
submitted to the FDA. First, the authors indicated that stenosis was dose-
dependent and observed that patients with a longer duration and higher
cumulative dose of docetaxel were significantly more likely to exhibit complete
134 Id.
135 Doc. 445-26 at 2 (emphasis added).
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canalicular closure. Contrary to Sanofi’s assertion, such evidence is not merely
cumulative evidence and/or further evidence of a causal connection.136 Rather,
as Plaintiffs argue, these observations—coupled with the authors’ emphasis on
the need for monitoring, early detection and/or surgical intervention—provide
at least some evidence about the progressiveness of the injury.
While the authors of the 2001 Esmaeli Article and 2000 Kneuper Hall
Abstract reported on similar injuries and surgical interventions and penned
similar warnings regarding the need for referral to an ophthalmologist and/or
prompt intervention, those warnings were based on a handful of reports and
provided 	with 	little 	context, 	and 	the 	Hall 	Abstract 	was 	focused 	on
“canaliculitis,” rather than only on stenosis. At minimum, the 2003 Esmaeli
Article provided further analysis on an injury that—according to the 2001
Esmaeli Article—had not been reported in any literature prior to 2001 and
whose mechanism remained unclear.
Second, the authors of the 2003 Esmaeli Cancer Study found that
stenosis occurred even in the neoadjuvant setting, where the drug is used for
a limited time. Neither the Hall Abstract nor the 2001 Esmaeli Article reported
on patients in this setting. They noted that “the role of weekly taxanes in the
neoadjuvant 	setting 	is 	becoming 	better 	established,” 	and 	opined 	that
136 See In re Zofran, 57 F.4th at 339 (finding that certain animal studies, which
differed in dose from prior animal studies, were not “newly acquired information” because,
among other things, the studies indicated that the observed anomalies in the animal subjects
were “not dose related” and/or “had no dose-dependency”). Sanofi contends that this is not a
“no warnings case,” so evidence about a stronger causal connection, standing alone, is not
“newly acquired information.” But even assuming the 2003 Study only provides evidence
about a causal connection, Plaintiffs point out that the warning at issue was never in the
Warnings and Precautions section (or pre-2006 equivalent).
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“[b]ecause patients receiving adjuvant docetaxel have a longer life expectancy
than patients receiving docetaxel in the metastatic setting, it is especially
crucial to recognize canalicular obstruction early and offer the appropriate
therapy in patients receiving adjuvant docetaxel.”137 The authors noted that
the “[f]ailure to recognize canalicular obstruction early can leave patients with
no options except DCR with Pyrex glass tube placement, an inferior option.”138
They further noted that “in patients treated with weekly administration of
docetaxel, 	a 	regimen 	rarely 	associated 	with 	neutropenia 	and
thrombocytopenia, it is safe to perform surgery while the patient continues to
receive the previously planned chemotherapy regimen.”139
Finally, although the 2003 Study apparently did not provide sufficient
information from which an incidence rate could be determined (because only
patients with epiphora were evaluated), the authors’ pronouncement that
stenosis was a common and important side effect arguably indicated an uptick
in cases since Sanofi’s rough estimate of 1/10,000 cases of “tearing abnormality
requiring intervention” and/or “tear duct obstruction.”140
137 Doc. 445-26 at 4.
138 Id.
139 Dr. Esmaeli states in her Report that medical oncologists “occasionally used weekly
infusion cycles because of dose-limiting neutropenia, which is a life-threatening complication,
that can be seen when administered every three weeks.” Doc. 445-27 at 13.
140 See Wyeth, 555 U.S. at 570 (holding that as adverse incidents continued to occur,
the manufacturer “could have analyzed the accumulating data and added a stronger
warning”). Sanofi argues that frequency is not relevant here because Plaintiffs do not
explicitly argue that frequency was an issue on the label, as evidenced by their expert’s
opinion. The Court declines Sanofi’s invitation to address label adequacy here. The narrower
question before the Court is whether federal law preempts Plaintiffs’ state-law failure-to-
warn claims.
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As the First Circuit has explained, “[t]he CBE regulation covers virtually
all situations in which new information indicates new or greater risks.”141 To
be sure, the authors of the 2003 Study noted that they were reporting on their
“expanded experience with epiphora and canalicular and nasolacrimal duct
blockage,” thus indicating that some of the data was not “new.”142 Notably,
however, the authors also opined that they “frequently encounter[ed] advanced
cases 	of 	this 	condition 	because 	of 	delayed 	diagnosis. 	Thus, 	it 	appears
oncologists need to be become better educated regarding this side effect.”143
The authors also found it important to state that “in our opinion, canalicular
stenosis may be the most important side effect of weekly docetaxel.”144
At bottom, as the Supreme Court has made clear, the CBE regulation
accounts for the fact that “risk information accumulates over time and that
same 	data 	may 	take 	on 	a 	different 	meaning 	in 	light 	of 	subsequent
developments.”145 The same is true here. The Court finds that the 2003 Esmaeli
Study 	constitutes 	“newly 	acquired 	information.”146 	Accordingly, 	the 	CBE
141 In re Celexa, 779 F.3d at 41.
142 Doc. 445-26 at 3.
143 Id. at 5.
144 Id.
145 Wyeth, 555 U.S. at 569.
146 Although it need look no further, the Court notes that at least one additional piece
of literature constitutes “newly acquired information.” In the 2001 Esmaeli Article, the
authors noted that a “prospective study” was “currently underway at our institution to
evaluate the incidence of canalicular stenosis secondary to docetaxel and the relationship
between dosing and frequency of administration of this drug and the incidence of this form
of toxicity.” Doc. 445-10 at 22. In 2006, Dr. Esmaeli and others published a study titled
“Prospective Study of Incidence and Severity of Epiphora and Canalicular Stenosis in
Patients with Metastatic Breast Cancer Receiving Docetaxel” in the Journal of Clinical
Oncology. Doc. 493-120. The Study, which was sponsored by Sanofi to meet an “unmet
medical need,” was conducted to “determine the incidence and severity of epiphora and
canalicular stenosis in patients receiving docetaxel weekly or every 3 weeks,” and appears to
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regulation 	was 	available 	for 	Sanofi 	to 	change 	its 	label, 	and 	it 	was 	not
impossible 	for 	Sanofi 	to 	comply 	with 	both 	state 	and 	federal 	obligations.
Plaintiffs’ 	claims 	are 	therefore 	not 	preempted 	under 	impossibility
preemption.147
CONCLUSION
For the foregoing reasons, Sanofi’s Motion for Summary Judgment is
DENIED.
New Orleans, Louisiana this 1st day of December, 2025.
____________________________________
JANE TRICHE MILAZZO
UNITED STATES DISTRICT JUDGE
be the one of the first prospective studies examining incidence rates of stenosis, as well
surgical outcomes. Id. at 2. In her Report, Dr. Esmaeli states that this “important research
article” was published in “arguably one of the highest impact journals read by medical
oncologists throughout the world.” Doc. 441-2 at 18.
147 As explained above, Sanofi does not move for summary judgment on the issue of
“clear evidence”; nor does it argue that the CBE regulation’s causal association requirement
is not satisfied.
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