Gaeta v. Perrigo Pharmaceuticals Co.

FOR PUBLICATION
UNITED STATES COURT OF APPEALS
FOR THE NINTH CIRCUIT

MARGARITA GAETA, as guardian ad 
litem for A.G., a minor child;
AUGUSTINE GAETA, No. 09-15001
Plaintiffs-Appellants,

D.C. No.
v. 5:05-cv-04115-JW
PERRIGO PHARMACEUTICALS OPINION
COMPANY; BASF CORPORATION,
Defendants-Appellees.

Appeal from the United States District Court
for the Northern District of California
James Ware, District Judge, Presiding

Argued and Submitted
October 6, 2010—San Francisco, California

Filed January 24, 2011

Before: David R. Thompson, Ferdinand F. Fernandez and
Barry G. Silverman, Circuit Judges.

Opinion by Judge Thompson

1371
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1375
COUNSEL

Brian D. Witzer and Rowena J. Dizon of Law Offices of
Brian D. Witzer, Inc., West Hollywood, California, for the
plaintiffs-appellants.

Michael F. Healy and Kelly S. Day of Sedgwick, Detert,
Moran & Arnold LLP, San Francisco, California, for the
defendants-appellees.

OPINION

THOMPSON, Senior Circuit Judge:

Plaintiffs-appellants Margaret Gaeta, as guardian ad litem
for A.G., a minor child, and Augustine Gaeta (collectively,
“the Gaetas”) appeal the district court’s grant of summary
judgment in favor of Perrigo Pharmaceutical Company. The
district court determined that the Gaetas’ state law failure-to-
warn claims against Perrigo, a manufacturer of a generic ver-
sion of ibuprofen, were preempted under federal law. Subse-
quently, the Supreme Court decided Wyeth v. Levine, 129 S.
Ct. 1187 (2009), and determined that state law failure-to-warn
claims against brand name manufacturers were not preempted
by federal law. The district court, however, denied the Gaetas’
motion for reconsideration, concluding that Levine does not
govern whether federal law preempts similar claims against
generic manufacturers.

Since then, two Courts of Appeals and all of the district
courts to consider the issue have held otherwise, using the
rationale underlying Levine to find that federal law does not
preempt state law failure-to-warn claims against generic man-
ufacturers, provided there is no “clear evidence” that the FDA
would not have approved the proposed stronger warning. We
agree and hold that the district court erred in applying federal
preemption. Accordingly, we reverse and remand.
1376 GAETA v. PERRIGO PHARMACEUTICALS CO.
I

On June 3, 2004, A.G. had two benign moles removed in
a surgical procedure. During the procedure, A.G. received
Halothane, an anesthetic known to be “hepatotoxic”—that is,
to cause liver failure in certain circumstances. After the sur-
gery, A.G. was discharged with a prescription for ibuprofen
and instructions to take one 400mg tablet once every six hours
as needed for pain. Instead, A.G.’s parents purchased Perri-
go’s generic over-the-counter (“OTC”) ibuprofen at 200mg
per tablet. For the next four days, A.G. took 400mg of the
generic ibuprofen every six to eight hours.

On June 11, 2004, A.G. developed a fever and was seen by
his pediatrician, who prescribed prescription-strength ibu-
profen (400mg). However, A.G.’s condition continued to
worsen, and on June 13, 2004, he was referred to the emer-
gency room with a diagnosis of septic shock, dehydration, and
liver failure. He was later transferred to Stanford University
Hospital for a liver transplant, which took place on June 15,
2004. A.G. also developed other complications, and he even-
tually required amputation of necrotic tissue on his fingers
and toes.

The Gaetas filed suit against Perrigo and several other man-
ufacturers of generic ibuprofen, alleging defective design,
defective marketing, breach of express and implied warranty,
negligence and gross negligence, and deceit by concealment.1
Prevalent in all of the Gaetas’ claims is the allegation that the
generic manufacturers failed to warn prescribing physicians
and consumers of the increased risk of acute liver injury and
renal (i.e., kidney) failure when ibuprofen is taken concur-
rently with other drugs known to be hepatotoxic.
1
The Gaetas have either settled with or dismissed all of the manufactur-
ers except Perrigo.
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1377
Perrigo moved for summary judgment on preemption
grounds, arguing that the Gaetas’ state law failure-to-warn
claims conflicted with FDA regulations relating to the label-
ing and marketing of generic drugs. The district court agreed,
and concluded that the Gaetas’ claims were preempted
because a generic manufacturer could not comply with the
heightened state law warning requirements without running
afoul of the FDA regulations requiring generic drug labels to
conform to the approved labeling for brand name drugs. The
district court granted summary judgment in favor of Perrigo,
and the Gaetas appealed.

The Supreme Court subsequently decided Levine, 129 S.
Ct. 1187. In light of Levine, the Gaetas obtained a limited
remand from this court to allow the district court to consider
a post-judgment motion for reconsideration. The district
court, however, denied the motion for reconsideration, con-
cluding that the Court’s holding in Levine that the FDA regu-
lations do not preempt state tort law claims for inadequate
labeling against brand name manufacturers does not govern
whether the FDA regulations preempt similar claims against
generic manufacturers.

II

We review de novo an order granting summary judgment.
Lopez v. Smith, 203 F.3d 1122, 1131 (9th Cir. 2000) (en
banc). We must determine “whether, viewing the evidence in
the light most favorable to the nonmoving party, there are any
genuine issues of material fact and whether the district court
correctly applied the relevant substantive law.” Id. (citation
omitted).

III

[1] This appeal presents an issue of first impression for our
court. We must determine what effect, if any, the Supreme
Court’s decision in Levine has on the question whether appli-
1378 GAETA v. PERRIGO PHARMACEUTICALS CO.
cable FDA regulations preempt state tort law claims for inad-
equate labeling against generic—as opposed to brand name—
manufacturers. In resolving this question, we consider a brief
history of federal drug regulation and labeling.

A. The FDA’s Regulation of Drugs

In the 1930’s, Congress became “increasingly concerned
about unsafe drugs and fraudulent marketing,” Levine, 129 S.
Ct. at 1195, and enacted the Federal Food, Drug, and Cos-
metic Act (“FDCA”). See 21 U.S.C. § 301 et seq. The FDCA
required every manufacturer to submit a new drug application
(“NDA”), including reports of investigations and specimens
of proposed labeling, to the FDA before any new drug could
be marketed and sold to the public. 21 U.S.C. § 355(b). In
1962, Congress amended the FDCA and shifted the burden of
proof from the FDA to the manufacturer. Levine, 129 S. Ct.
at 1195. These amendments, which are still in effect, require
the manufacturer to demonstrate that its drug is “safe” and
“effective” before the drug can be distributed. Id.; see also 21
U.S.C. § 355(b). Once the drug covered by the NDA is
approved for safety and effectiveness, that drug—also
referred to as the “listed drug”—may be sold to consumers
under the NDA holder’s brand name.

A less demanding approval process applies to manufactur-
ers seeking to market generic drugs. In 1984, Congress passed
the Hatch-Waxman Amendments to the FDCA, which pro-
vided that once a brand name drug’s NDA is approved and
the drug is officially listed by the FDA, any manufacturer
may seek permission to market a generic version of that drug
by submitting an abbreviated NDA (“ANDA”). See Drug
Price Competition and Patent Term Restoration Act of 1984,
Pub. L. No. 98-417, 98 Stat. 1585 (1984). Under the Hatch-
Waxman Amendments, generic manufacturers need not repeat
the clinical work of their brand name counterparts, but rather
must establish that except for enumerated differences irrele-
vant here, their drug is the “same as” the brand name drug
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1379
that has already been approved by the FDA as to active ingre-
dients, route of administration, dosage form, strength, and
conditions of recommended use specified on the label. 21
U.S.C. § 355(j)(2)(A). By avoiding unnecessary duplication
of previously-performed clinical trials, Congress sought to
accelerate the availability of low-cost drugs, thereby resulting
in significant cost savings to the American public.2

ANDA applicants must also show that the labeling pro-
posed for a new generic drug is the “same as” the labeling
approved for the listed drug. 21 U.S.C. § 355(j)(2)(A)(v),
(j)(4)(G). At any time after a new generic drug is approved,
the FDA reserves the right to withdraw approval if it deter-
mines that the generic drug’s labeling is “no longer consis-
tent” with that of the listed drug. 21 C.F.R. § 314.150(b)(10).
Moreover, the FDCA prohibits all manufacturers from distrib-
uting a “misbranded” drug, 21 U.S.C. § 331(a)-(b), including
a drug whose “labeling is false or misleading in any particu-
lar.” See 21 U.S.C. § 352(a). The FDA has enforcement
mechanisms to ensure that drugs with misleading labels are
taken off the market. See 21 U.S.C. §§ 333, 355(e).

B. The Supreme Court’s Decision in Wyeth v. Levine

In Levine, the plaintiff, Diana Levine, brought suit against
a drug manufacturer, Wyeth, when she developed gangrene
after receiving an IV-push injection of Phenergan, Wyeth’s
brand name for an antihistamine used to treat nausea. 129 S.
Ct. at 1191. Levine asserted state tort law claims against
Wyeth alleging that Phenergan’s labeling was defective
because, although it warned of the danger of gangrene and
amputation following inadvertent intra-arterial injection, the
label failed to warn against the use of the IV-push method for
2
For example, generic drugs saved American consumers between
approximately $8 billion and $10 billion in 1994. CONGRESSIONAL BUDGET
OFFICE, HOW INCREASED COMPETITION FROM GENERIC DRUGS HAS AFFECTED
PRICES AND RETURNS IN THE PHARMACEUTICAL INDUSTRY 13 (July 1998).
1380 GAETA v. PERRIGO PHARMACEUTICALS CO.
administering the drug, which posed a higher risk than the IV-
drip method. Id. at 1191-92.

The Supreme Court upheld the trial court’s refusal to over-
turn on preemption grounds the jury’s verdict in favor of
Levine. Id. at 1204.

Wyeth contended it would have been impossible for it to
comply with the state-law duty to modify Phenergan’s label-
ing without violating federal law. Id. at 1196. The Court
rejected this argument, concluding that because FDA regula-
tions permit drug manufacturers to make certain changes to
their labels without prior FDA approval, Wyeth could have
met its state-law obligation to provide additional warnings
without violating FDA labeling requirements. Id. at 1196-99.
Specifically, the Court determined that Wyeth could have uti-
lized the FDCA’s changes being effected (“CBE”) regulation,
which permits drug manufacturers to change a label, without
prior FDA approval, to “add or strengthen a contraindication,
warning, precaution, or adverse reaction,” 21 C.F.R.
§ 314.70(c)(6)(iii)(A) (2004), or to “add or strengthen an
instruction about dosage and administration that is intended to
increase the safe use of the drug product,” 21 C.F.R.
§ 314.70(c)(6)(iii)(C). Levine, 129 S. Ct. at 1196-99.

Next, the Court concluded there was no merit to Wyeth’s
contention that Levine’s state tort claims were preempted
because they interfered with Congress’ purpose to entrust the
FDA with making drug labeling decisions. Id. at 1199. In
doing so, the Court noted that Congress had repeatedly
declined to preempt state law in the field of prescription
drugs. Id. at 1200. The Court also concluded that the FDA’s
unilateral assertion of broad preemption power in this area,
see 71 Fed. Reg. 3922, 3934-35 (Jan. 24, 2006), was entitled
to no weight. Id. at 1200-04. According to the Court, because
manufacturers have “superior access to information” about
their drugs than does the FDA, especially in the post-
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1381
marketing phase as new risks emerge, they “bear primary
responsibility for their drug labeling at all times.” Id. at 1202.

[2] The focal issue in this appeal is whether the Court’s
holding in Levine—that the federal regulatory regime govern-
ing pharmaceuticals does not preempt state law failure-to-
warn claims against brand name manufacturers—extends with
equal force to claims against generic manufacturers.3 As
explained below, today we join the Fifth and Eighth Circuits
in concluding that, while not dispositive, Levine does fore-
shadow a similar disposition in this case. See Demahy v.
Actavis, Inc., 593 F.3d 428, 430 (5th Cir. 2010), cert. granted,
78 U.S.L.W. 3745 (U.S. Dec. 10, 2010) (No. 09-1501); Mens-
ing v. Wyeth, Inc., 588 F.3d 603, 607 (8th Cir. 2009), cert.
granted, 78 U.S.L.W. 3522 (U.S. Dec. 10, 2010) (No. 09-
993), and cert. granted, 78 U.S.L.W. 3523 (U.S. Dec. 10,
2010) (No. 09-1039).

C. Preemption Analysis

In considering a federal preemption defense, we are guided
by two important considerations. First, “ ‘the purpose of Con-
gress is the ultimate touchstone in every pre-emption case.’ ”
Levine, 129 S. Ct. at 1194 (quoting Medtronic, Inc. v. Lohr,
518 U.S. 470, 485 (1996)). Second, we must apply the pre-
sumption against preemption, especially when “Congress has
legislated . . . in a field which the States have traditionally
occupied.” Id. (quoting Lohr, 518 U.S. at 485) (internal quota-
tion marks omitted). As the Supreme Court explained, “[w]e
rely on the presumption because respect for the States as
‘independent sovereigns in our federal system’ leads us to
assume that ‘Congress does not cavalierly pre-empt state-law
causes of action.’ ” Id. at 1195 n.3 (quoting Lohr, 518 U.S. at
485).
3
We note that the issues of causation and whether there was additional
evidence indicating the need for hepatotoxicity warnings with the OTC
use of ibuprofen are still highly disputed in this case. We leave those
issues for the district court to decide in the first instance.
1382 GAETA v. PERRIGO PHARMACEUTICALS CO.
[3] Under the Supremacy Clause, U.S. CONST. art. VI, cl.
2, Congressional intent to preempt state law can either be
expressed in statutory language or implied from the scheme
of federal regulation. Hillsborough Cnty., Fla. v. Automated
Med. Labs., Inc., 471 U.S. 707, 712-13 (1985). Implied pre-
emption comes in two forms: field and conflict preemption.
Field preemption occurs when the federal regulation is suffi-
ciently comprehensive to leave no room for supplementary
state regulation. Id. at 713. Conflict preemption, in turn, arises
when: (1) “ ‘compliance with both federal and state regula-
tions is a physical impossibility,’ ” or (2) “state law ‘stands as
an obstacle to the accomplishment and execution of the full
purposes and objectives of Congress.’ ” Id. (citations omit-
ted). The conflict might be with a federal statute or an
“agency regulation with the force of law.” Levine, 129 S. Ct.
at 1200.

In the present case, Perrigo contends the Gaetas’ claims are
conflict preempted because it is impossible for Perrigo to
comply with both the state-law duties to warn and the federal
regulatory regime governing generic drugs. Alternatively,
Perrigo contends that the Gaetas’ state law claims are conflict
preempted because they obstruct the full accomplishment of
the purposes and objectives of Congress in enacting the
Hatch-Waxman Amendments. We reject both contentions.

1. There is no impossibility of compliance.

Impossibility preemption is “a demanding defense.” Levine,
129 S. Ct. at 1199. In asking us to uphold the district court’s
finding of preemption, Perrigo in effect asks us to disregard
the underlying reasoning of Levine and to create an inter-
circuit split with respect to generic manufacturers’ liability for
inadequate labeling. We decline to do so.

[4] We agree with the Gaetas, and with our two sister cir-
cuits, that the FDCA provides generic manufacturers with at
least three separate mechanisms by which they can discharge
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1383
their state-law duty to warn of additional risks associated with
their products: (a) the CBE process approved by the Supreme
Court in Levine; (b) the “prior approval” process; and (c) by
asking the FDA to send “Dear Doctor” warning letters to
health care professionals.

Initially, there is no dispute between the parties that the
Hatch-Waxman Amendments require an ANDA applicant to
use a drug label that is the “same as” that approved for the
listed drug. See 21 U.S.C. § 355(j)(2)(A)(v), (j)(4)(G). The
only dispute is whether ANDA holders must similarly comply
with that requirement after their applications have been
approved. Perrigo contends that they do and points to 21
C.F.R. § 314.150(b)(10), which allows the FDA to withdraw
approval if the agency finds that the drug’s labeling is “no
longer consistent” with that for the listed drug, and 21 U.S.C.
§ 352(a), which prohibits the manufacture and distribution of
any “misbranded” drug. However, the fact that a generic
drug’s label must remain “consistent” with that for the listed
drug does not mean that the two labels must be “identical.” In
other words, just because a generic drug’s label has stronger
warnings than those on the label of its brand name counterpart
does not mean the two labels lack consistency. For example,
the Supreme Court in Levine found it “difficult to accept” that
the FDA would bring an enforcement action against a manu-
facturer for strengthening a warning on a drug’s label. 129 S.
Ct. at 1197. Similarly, the Court noted that a drug is not mis-
branded “simply because the manufacturer has altered an
FDA-approved label.” Id. Instead, “the misbranding provision
focuses on the substance of the label” and in fact “proscribes
labels that fail to include ‘adequate warnings.’ ” Id. (quoting
21 U.S.C. § 352(f)) (emphasis added); accord Demahy, 593
F.3d at 439 (“[R]ather, the misbranding provisions concern
the accuracy of the label’s substance and the adequacy of its
warnings . . . .” (citations omitted)).

[5] Indeed, the regulatory framework makes clear that
generic manufacturers, just like their brand name counter-
1384 GAETA v. PERRIGO PHARMACEUTICALS CO.
parts, must take specific steps when they learn of new risks
associated with their products. Thus, both sets of manufactur-
ers must record and report to the FDA certain adverse effects.
See 21 C.F.R. § 314.80(a), (c) (NDA holders); 21 C.F.R.
§ 314.98(a) (ANDA holders). Similarly, both sets of manufac-
turers must submit annual reports that include, inter alia, a
“brief summary of significant new information from the pre-
vious year that might affect the safety, effectiveness, or label-
ing of the drug product” and a “brief description of actions the
applicant has taken or intends to take as a result of this new
information, for example, submit a labeling supplement, add
a warning to the labeling, or initiate a new study.” 21 C.F.R.
§ 314.81(b)(2)(I) (NDA holders); 21 C.F.R. § 314.98(c)
(ANDA holders).

[6] Based on these adverse reports, drug manufacturers
“shall” revise their drug labeling to include a warning “as
soon as there is reasonable evidence of an association of a
serious hazard with a drug; a causal relationship need not
have been proved.” 21 C.F.R. § 201.57(e) (2004).4 And even
though the FDA is the final arbiter of whether any such label-
ing revision is appropriate, the “primary responsibility” for
the label’s adequacy always remains with the drug manufac-
turer. Levine, 129 S. Ct. at 1202; see also id. at 1197-98 (“[I]t
has remained a central premise of federal drug regulation that
the manufacturer bears the responsibility for the content of its
label at all times.”).

i. A generic manufacturer can utilize the CBE process
to make changes to its label without any prior
approval by the FDA.

Generally speaking, FDA approval is necessary before a
manufacturer may change a drug label. 21 C.F.R.
§ 314.70(b)(2)(v)(A). As one exception, however, the CBE
4
This version of the regulation was in effect when A.G.’s injury took
place. Today, this provision is codified in 21 C.F.R. § 201.80(e).
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1385
provision allows a drug manufacturer to make a label change
that becomes effective immediately upon the FDA’s receipt of
the supplemental application for the change. 21 C.F.R.
§ 314.70(c)(6)(iii). A drug manufacturer can utilize the CBE
process to strengthen its warnings when doing so is necessary
“to reflect newly acquired information.” 21 C.F.R.
§ 314.70(c)(6)(iii)(A), (C). As the Court explained in Levine,
in this context, the “newly acquired information” is not lim-
ited to new data, but “also encompasses ‘new analyses of pre-
viously submitted data.’ ” 129 S. Ct. at 1197 (quoting 73 Fed.
Reg. 49603, 49604 (Aug. 22, 2008)). As such, this rule “ac-
counts for the fact that risk information accumulates over time
and that the same data may take on a different meaning in
light of subsequent developments.” Id.

[7] Nothing in the text of the Hatch-Waxman Amendments
forbids an ANDA holder from utilizing the CBE process.
Indeed, the opposite is true. The CBE provision is contained
in 21 C.F.R. § 314.70, which is located in Subpart B of the
Regulations (entitled, “Applications”) and which admittedly
deals only with applications for the listed drugs. However,
§ 314.70 is expressly made applicable to ANDA holders by
operation of 21 C.F.R. § 314.97, which is located in Subpart
C of the Regulations (entitled, “Abbreviated Applications”)
and provides that ANDA applicants “shall comply with the
requirements of §§ 314.70 and 314.71 regarding the submis-
sion of supplemental applications and other changes to an
approved abbreviated application” (emphasis added).5
5
Relying on Morris v. Wyeth, Inc., 642 F. Supp. 2d 677 (W.D. Ky.
2009), appeal docketed, No. 09-5509 (6th Cir. Apr. 27, 2009), Perrigo
proposes an alternate way to read 21 C.F.R. § 314.97. According to this
view, Ҥ 314.97 merely states that when a brand [name] manufacturer uti-
lizes § 314.70, then so too must the generic manufacturer make that same
change to its corresponding drug’s label.” Morris, 642 F. Supp. 2d at 685
(denying reconsideration of the court’s prior order finding plaintiff’s
failure-to-warn claims against generic manufacturers to be preempted). In
other words, according to Perrigo, § 314.97 is merely a restatement of the
initial requirement prior to approval that the labeling for a generic drug
1386 GAETA v. PERRIGO PHARMACEUTICALS CO.
All but one of the courts to consider this issue after Levine
have concluded that the CBE process is available to generic
manufacturers on the same terms as to brand name manufactur-
ers.6 Indeed, except for the district court’s decision in this
case, Perrigo cannot point to any post-Levine decision con-

must be the “same as” that of the brand name equivalent, no more and no
less.
This, however, is a very strained reading of § 314.97. As the Fifth Cir-
cuit observed in addressing the same question, had the FDA intended to
deny generic manufacturers access to the CBE process despite § 314.97’s
plain language, we might expect the FDA to say so, either in § 314.97 or
§ 314.70. See Demahy, 593 F.3d at 441. The FDA has not done so, how-
ever, and we decline to imply such a constricting limitation ourselves.
Rather, on the face of the regulations in effect, generic manufacturers must
comply with the provisions of § 314.70 and maintain adequate warnings.
See Demahy, 593 F.3d at 441-42; Mensing, 588 F.3d at 611.
6
See, e.g., Demahy, 593 F.3d at 439-41 (concluding that the CBE pro-
cess is available to generic manufacturers); Dorsett v. Sandoz, Inc., 699 F.
Supp. 2d 1142, 1160-62 (C.D. Cal. 2010) (same); Munroe v. Barr Labs.,
Inc., 670 F. Supp. 2d 1299, 1302-03 (N.D. Fla. 2009) (same); Bartlett v.
Mut. Pharm. Co., 659 F. Supp. 2d 279, 296-99 (D.N.H. 2009) (same); Sta-
cel v. Teva Pharm., USA, 620 F. Supp. 2d 899, 905 (N.D. Ill. 2009)
(same). The Fourth Circuit reached a similar conclusion more than 15
years ago. See Foster v. Am. Home Prods. Corp., 29 F.3d 165, 170 (4th
Cir. 1994) (“Although generic manufacturers must include the same label-
ing information as the equivalent name brand drug, they are also permitted
to add or strengthen warnings and delete misleading statements on labels,
even without prior FDA approval.” (citing 21 C.F.R. § 314.70 (1993))).
The only post-Levine case to consider the issue and reach a different
conclusion was the district court’s decision in this case. See Gaeta v. Per-
rigo Pharm. Co., 672 F. Supp. 2d 1017, 1021-22 (N.D. Cal. 2009). In
addition, on the day Levine was decided, Judge Russell of the Western
District of Kentucky entered minute orders reaffirming in light of Levine
his findings of preemption of warning claims in three related cases involv-
ing generic Reglan. See Smith v. Wyeth, Inc., No. 5:07-CV-18-R, 2009
WL 736208 (W.D. Ky. Mar. 4, 2009); Morris v. Wyeth, Inc., No. 1:07-
CV-176-R, 2009 WL 736200 (W.D. Ky. Mar. 4, 2009); Wilson v. Wyeth,
Inc., No. 3:07-CV-00378-R, 2009 WL 736198 (W.D. Ky. Mar. 4, 2009).
These three cases are currently in a consolidated appeal before the Sixth
Circuit.
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1387
cluding otherwise.7 Neither can Perrigo point to any authorita-
tive statement from the FDA to the contrary. While previously
Perrigo could rely on the FDA’s assertion that “under existing
preemption principles, FDA approval of labeling under the act
. . . preempts conflicting or contrary State law,” 71 Fed. Reg.
3922, 3934, that pronouncement is entitled to no weight after
Levine. See 129 S. Ct. at 1201 (finding FDA’s view on pre-
emption unsupported by evidence and “inherently suspect,”
and concluding that it “does not merit deference”). Similarly,
Perrigo receives little help from a footnote in the FDA’s 2008
proposed rule to amend § 314.70, which provides:

CBE changes are not available for generic drugs
approved under an abbreviated new drug application
under 21 U.S.C. 355(j). To the contrary, a generic
drug manufacturer is required to conform to the
approved labeling for the listed drug. See 21 CFR
314.150(b)(10); see also 57 FR 17950, 17953, and
17961.

73 Fed. Reg. 2848, 2849 n.1 (Jan. 16, 2008). As Perrigo itself
concedes, the final version of the rule omits this footnote’s
language. See generally 73 Fed. Reg. 49603 (Aug. 22, 2008).
Having been abandoned, the FDA’s earlier position is “de-
prived of all claim to deference[ ] by the fact that it is no lon-
ger the agency’s position.” Riegel v. Medtronic, Inc., 552 U.S.
312, 327 (2008); accord Demahy, 593 F.3d at 444.
7
In reaching its conclusion, the district court in this case relied on an
apparent “split of opinion” among pre-Levine cases. See Gaeta, 672 F.
Supp. 2d at 1021 & n.4. However, of the two decisions cited by the district
court for the proposition that “a generic drug manufacturer may not unilat-
erally strengthen a drug label without prior FDA approval,” id. at 1021
n.4, one has since been reversed on appeal, see Mensing v. Wyeth, 562 F.
Supp. 2d 1056 (D. Minn. 2008), rev’d, 588 F.3d 603, and the other relied
on the first in reaching its conclusion, see Morris v. Wyeth, 582 F. Supp.
2d 861, 867-68 (W.D. Ky. 2008), reconsideration denied, 642 F. Supp. 2d
677, appeal docketed, No. 09-5509 (6th Cir. Apr. 27, 2009). Accordingly,
at this stage, these decisions provide little, if any, support for the district
court’s conclusion in this case.
1388 GAETA v. PERRIGO PHARMACEUTICALS CO.
Perrigo’s arguments in opposition are not persuasive. For
example, Perrigo argues that because it has never received,
nor attempted to withhold, any information suggesting the use
of its product contributed to or caused liver damage, “there
was nothing [for it] to report to the FDA to support plaintiffs’
proposed label change.” Underlying the Gaetas’ claims, how-
ever, are allegations that Perrigo should have followed—but
did not—the same record keeping and reporting of adverse
drug experiences post-marketing that brand name manufactur-
ers must undertake. See 21 C.F.R. § 314.98. As part of that
record keeping, the FDA requires ANDA holders to “develop
written procedures for the surveillance, receipt, evaluation,
and reporting of postmarketing adverse drug experiences to
FDA.” See 21 C.F.R. §§ 314.80(b), 314.98(a). And if any new
information becomes available, the FDA requires ANDA
holders to report what actions they have taken or intend to
take as a result of this information, “for example, submit a
labeling supplement, add a warning to the labeling, or initiate
a new study.” 21 C.F.R. § 314.81(b)(2)(I); 21 C.F.R.
§ 314.98(c).

[8] Similarly, Perrigo argues that any claim that it failed to
fulfill its duty to supply information to the FDA is a question
for the FDA and not the court, and as such is preempted under
Buckman Co. v. Plaintiffs’ Legal Comm., 531 U.S. 341, 347-
51 (2001) (finding plaintiffs’ state-law “fraud-on-the-FDA”
claims to be preempted). Buckman, however, is not applicable
in this context. The question before us is not whether Perrigo
provided inaccurate or incomplete information to the FDA,
but rather whether it complied with its post-marketing obliga-
tions to warn consumers and health care professionals about
additional risks associated with its product. Because these
claims are based on Perrigo’s alleged violation of its state-law
duties rather than an alleged violation of the FDCA itself,
they are not preempted under Buckman.
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1389
ii. A generic manufacturer can also utilize the “prior
approval” process to propose a labeling change to
the FDA that, if accepted, would be imposed uni-
formly on both sets of manufacturers.

Even were the CBE process unavailable to generic manu-
facturers, nothing in the FDCA or the Hatch-Waxman
Amendments prohibits such a manufacturer from proposing a
label change through the “prior approval” process. See 21
C.F.R. § 314.70(b)(2)(v). Unlike the CBE process, the “prior
approval” process requires the FDA’s approval of the supple-
mental application before the change can be effected. Id.
Moreover, by using the prior approval process, a generic man-
ufacturer would not have to worry about its labeling not being
“consistent” with that of the listed drug because, if the FDA
were to accept the proposed change, it would be imposed uni-
formly on both sets of manufacturers. See 57 Fed. Reg.
17950, 17961 (Apr. 28, 1992).

[9] Indeed, it appears the FDA itself envisioned the possi-
bility that ANDA holders would utilize the “prior approval”
process to suggest new warnings to the FDA. Thus, in its
commentary submitted in connection with the 1992 final rule,
the FDA expressly stated that “[a]fter approval of an ANDA,
if an ANDA holder believes that new safety information
should be added, it should provide adequate supporting infor-
mation to FDA, and FDA will determine whether the labeling
for the generic and listed drugs should be revised.” Id.
(emphases added). Nothing prevented Perrigo from seeking a
prior approval from the FDA for a label change.

iii. A generic manufacturer can also request that the
FDA send “Dear Doctor” warning letters to health
care professionals.

[10] In addition to proposing a label change, Perrigo could
have suggested that the FDA send a “Dear Doctor” letter to
heath care professionals, warning them of the risks associated
1390 GAETA v. PERRIGO PHARMACEUTICALS CO.
with using ibuprofen concurrently with other drugs known to
be hepatotoxic. See 21 C.F.R. § 200.5.

When the FDA first adopted its labeling regulations, well
before the Hatch-Waxman Amendments, it made clear that
the labeling requirements “do not prohibit a manufacturer . . .
from warning health care professionals whenever possibly
harmful adverse effects associated with the use of the drug are
discovered.” 44 Fed. Reg. 37434, 37447 (June 26, 1979).
Although such letters are considered regulated “labeling,” see
21 C.F.R. § 202.1(l)(2), Perrigo could have asked the FDA to
send them on its behalf. See 21 U.S.C. § 355-1(i)(2)(A) (pro-
viding that the FDA will send a letter to health care providers
on behalf of an ANDA holder if such letter is a necessary part
of a risk evaluation and mitigation strategy).

[11] As Levine reaffirmed, drug manufacturers bear pri-
mary responsibility for maintaining their labels consistent
with safe and effective use of their products. In the present
case, Perrigo could have used at least one of the above three
mechanisms to warn consumers and health care professionals
of the risks associated with using ibuprofen concurrently with
other drugs known to be hepatotoxic. Accordingly, compli-
ance with both the state-law duty to warn and federal law was
not impossible.

2. There is no “clear evidence” that the FDA considered
and rejected stronger warnings than those proposed by
the Gaetas.

[12] Alternatively, to show that compliance was impossi-
ble, Perrigo argues the FDA considered and rejected the liver
warnings that the Gaetas claim Perrigo should have provided.
In Levine, the Supreme Court left open the possibility that
there could be preemption if a manufacturer was able to dem-
onstrate, by clear evidence, that the FDA would not have
approved the change to the drug’s label proposed by the plain-
tiff. 129 S. Ct. at 1198. The Court, however, did not clarify
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1391
what would amount to “clear evidence.” Rather, the only
guidance this court has is that the evidence presented in
Levine was insufficient to meet the clear evidence standard.
See, e.g., Mason v. Smithkline Beecham Corp., 596 F.3d 387,
391-92 (7th Cir. 2010) (using Levine as an “intellectual
anchor” to judge whether the evidence presented by the brand
name manufacturer amounted to “clear evidence”). Accord-
ingly, if there is evidence in this case less compelling than
there was in Levine, that the FDA would not have approved
the applicable label change, there is no preemption.

In Levine, Wyeth appealed from the jury’s determination
that it had failed to provide an adequate warning that directly
injecting Phenergan into a patient’s vein creates a significant
risk of catastrophic consequences. 129 S. Ct. at 1190-91. In
determining whether “clear evidence” of the FDA’s consider-
ation of the warning was presented, the Court focused on
whether Wyeth “attempted to give the kind of warning
required by the Vermont jury but was prohibited from doing
so by the FDA.” Id. at 1198.

The Court noted that in 1988, Wyeth did propose different
language for Phenergan’s warning about intra-arterial injec-
tion, adapted from revisions the FDA proposed in 1987, but
the FDA instructed Wyeth to retain the wording in its existing
label. Id. at 1198 n.5. The FDA apparently “did not regard the
proposed warning as substantively different” from the FDA-
approved warning. Id. The Court also noted that there was no
evidence in the record that either the FDA or Wyeth gave
more than “passing attention” to the precise issue in that case
—i.e., the difference between the IV-drip and the more dan-
gerous IV-push administration of Phenergan.8 Id. at 1198-99.
8
Indeed, the Levine majority criticized the dissent for “creatively
paraphras[ing] a few FDA orders” and thereby “conflating warnings about
IV-push administration and intra-arterial injection to suggest greater
agency attention to the question.” 129 S. Ct. at 1199 n.6 (internal citations
omitted).
1392 GAETA v. PERRIGO PHARMACEUTICALS CO.
Finally, the Court observed that Wyeth did not argue “that it
supplied the FDA with an evaluation or analysis concerning
the specific dangers posed by the IV-push method.” Id. at
1199. Accordingly, the Court concluded that Wyeth failed to
present clear evidence that the FDA would have prevented it
from adding a stronger warning about the IV-push method of
intravenous administration. Id.

With this in mind, we turn to the evidence presented by
Perrigo in this case. In the United States, ibuprofen has been
used as a prescription drug for the treatment of osteoarthritis
and rheumatoid arthritis since 1974. 67 Fed. Reg. 54139,
54139 (Aug. 21, 2002). The FDA approved the use of 200mg
ibuprofen as an OTC drug through the NDA process in 1984,
and as a generic drug in 1986. Id. at 54140-41. In 1987, Per-
rigo obtained approval to market its generic OTC ibuprofen.

In 2002, in response to a citizen petition, the FDA engaged
in a detailed review regarding the safety of ibuprofen.9 Id. at
54141-48. Based on this review, the FDA proposed adding
warnings to alert individuals of the potential for renal and gas-
trointestinal problems associated with ibuprofen. Id. at 54148.
In contrast, the FDA found there was limited clinical data
available to estimate the prevalence of hepatotoxicity with
OTC doses of ibuprofen. Id. at 54145-46. Accordingly, the
FDA concluded that there was “no need to propose a hepatitis
warning at this time.” Id. at 54146 (emphasis added).

Then, in 2006, the FDA considered what types of warnings
should be included for OTC internal analgesic, antipyretic,
and antirheumatic drug products, including ibuprofen. See 71
Fed. Reg. 77314 (Dec. 26, 2006). Based on its review, the
9
The citizen petition sought to have ibuprofen included as a generally
recognized safe and effective analgesic/antipyretic active ingredient for
OTC use. 67 Fed. Reg. 54139, 54140. The petition requested warnings
“specific for the OTC use of ibuprofen,” but did not request a specific
warning for liver toxicity. See id.
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1393
FDA concluded that additional warnings were necessary
regarding: (1) hepatotoxicity associated with acetaminophen,
and (2) gastrointestinal bleeding and renal toxicity associated
with aspirin and other nonsteroidal anti-inflammatory drugs.
See id. at 77316, 77323-24, 77327-28, 77331-33, 77340. No
warnings specific to hepatotoxicity due to ibuprofen use were
proposed or considered by the FDA at that time.

[13] The above two FDA reviews do not amount to “clear
evidence” that the FDA would not have approved the warn-
ings suggested by the Gaetas. Nowhere does Perrigo point to
any evidence that the FDA was presented with and actually
considered the risk of hepatotoxicity due to concomitant use
of ibuprofen and other drugs known to be hepatotoxic, which
is the specific warning requested by the Gaetas in this case.
See Levine, 129 S. Ct. at 1198 (focusing on whether the drug
manufacturer “attempted to give the kind of warning required
by the Vermont jury but was prohibited from doing so by the
FDA”). Rather, the only time the FDA actually considered
hepatotoxicity associated with the use of ibuprofen—as
opposed to acetaminophen—the FDA expressly concluded
that there was “no need to propose [such a] warning at this
time.” 67 Fed. Reg. 54139, 54146 (emphasis added). It is a
stretch to contend, as Perrigo does, that this amounts to clear
evidence that the FDA would have rejected the Gaetas’ pro-
posed hepatotoxicity warning two years later.

Nor does Perrigo suggest that it supplied the FDA with any
“evaluation or analysis concerning the specific dangers”
posed by such concomitant use, and that the FDA refused to
act. See Levine, 129 S. Ct. at 1199. Rather, both in 2002 and
2006, the only evidence before the FDA consisted of what
was submitted with the citizen petition in favor of including
ibuprofen as a safe drug as well as what the FDA itself had
reviewed or solicited from the industry and the public. See 71
Fed. Reg. 77314, 77316-17, 77328-29; 67 Fed. Reg. 54139,
54140-41. In this context, Perrigo’s insistence that the FDA
considered and rejected hepatotoxic warnings associated with
1394 GAETA v. PERRIGO PHARMACEUTICALS CO.
ibuprofen is—just like in Levine—nothing more than “cre-
ative[ ] paraphras[ing]” of the FDA’s regulations that “con-
flat[es] warnings” about the risk of hepatotoxicity associated
with acetaminophen and that associated with ibuprofen “to
suggest greater agency attention to the question.”10 See 129 S.
Ct. at 1199 n.6.

[14] Because the evidence presented by Perrigo in this case
is no more compelling than the evidence considered and
rejected by the Supreme Court in Levine, 129 S. Ct. at 1198-
99, we conclude that Perrigo did not meet its burden of dem-
onstrating by clear evidence that the FDA would have
rejected the Gaetas’ proposed label change.

3. There is no obstruction of purpose.

Even if compliance with state and federal law is not “im-
possible,” state claims may still be preempted if they
“ ‘stand[ ] as an obstacle to the accomplishment and execution
of the full purposes and objectives of Congress.’ ” Hillsbor-
ough Cnty., 471 U.S. at 713 (citation omitted). In this case,
Perrigo asserts that exposing generic manufacturers to liabil-
ity for inadequate warnings would either force them out of the
market or require them to raise prices to offset potential liabil-
ity costs, thereby thwarting the goal of the Hatch-Waxman
Amendments to deliver low cost generic drugs to consumers.
Perrigo also argues that requiring generic manufacturers to
place warnings on their products that do not appear on the
10
Perrigo also asserts that the FDA later “required the liver warning
plaintiffs seek on prescription-strength ibuprofen but not on OTC ibu-
profen,” which it argues implies that the FDA was aware of potential risks
but made a calculated decision to include the warning only on prescription
drugs. Perrigo, however, fails to provide any support for this assertion. In
any event, as the Gaetas argue, the conclusion to be drawn from this is
quite the opposite: the fact that the FDA later required these liver warnings
on prescription-strength ibuprofen suggests that the FDA might also have
accepted similar warnings for the OTC ibuprofen had Perrigo or any other
manufacturer suggested such warnings.
 GAETA v. PERRIGO PHARMACEUTICALS CO. 1395
corresponding brand name products would lead to loss of con-
sumer confidence in generic drugs, which consumers already
regard as being less safe and effective than the brand name
drugs.

[15] As to Perrigo’s first argument, there is no indication
that when Congress passed the Hatch-Waxman Amendments
it intended the goal of delivering low cost generic drugs to
supplant the FDCA’s overall goal of providing consumers
with safe and effective drugs. As both the Fifth and Eighth
Circuits have recognized, the Hatch-Waxman Amendments
must be considered as “part and parcel” of the FDCA, and not
as a separate statutory framework. See Demahy, 593 F.3d at
448; Mensing, 588 F.3d at 612. We join those two circuits in
concluding that while the Hatch-Waxman Amendments were
meant to provide an inexpensive and easy way for generic
drugs to enter the market, they were not intended as a relief
from the fundamental requirement of the FDCA that all mar-
keted drugs remain safe.

Indeed, in enlarging the FDA’s powers to protect the public
health and to assure the safety and effectiveness of drugs,
“Congress took care to preserve state law.” Levine, 129 S. Ct.
at 1195-96. “Evidently, [Congress] determined that widely
available state rights of action provided appropriate relief for
injured consumers.”11 Id. at 1199; see also Mensing, 588 F.3d
at 603 (“[W]e decline to assume that Congress intended to
shield from tort liability the manufacturers of the majority of
the prescription drugs consumed in this country and leave
11
As the Supreme Court observed, had Congress considered state-law
suits to be an obstacle to its objectives, “it surely would have enacted an
express pre-emption provision at some point during the FDCA’s 70-year
history.” Levine, 129 S. Ct. at 1200. But despite its 1976 enactment of an
express preemption provision for medical devices, Congress has not
enacted such a provision for the remainder of the FDCA. Id.; see also Rie-
gel, 552 U.S. at 327 (“Congress could have applied the pre-emption clause
to the entire FDCA. It did not do so, but instead wrote a pre-emption
clause that applies only to medical devices.”).
1396 GAETA v. PERRIGO PHARMACEUTICALS CO.
injured parties like Mensing no legal remedy.” (citing Foster,
29 F.3d at 170)). “If Congress had intended to deprive injured
parties of a long available form of compensation”—and to do
so in such an inconsistent manner—“it surely would have
expressed that intent more clearly.” Bates v. Dow Agro-
sciences LLC, 544 U.S. 431, 449 (2005) (citation omitted).

Perrigo’s argument that consumers will lose confidence in
generic drugs if they contain warnings different from those of
the brand name drugs also fails. First, it is purely speculative
that consumers will opt for a more expensive brand name
product—or against purchasing any product at all—if the less
expensive generic product contains additional warnings. Sec-
ond, as previously noted, there is no indication Congress
intended consumers to have access to low cost drugs at the
expense of safety. Finally, by using the “prior approval” pro-
cess, a generic manufacturer can avoid consumer confusion
because, if the FDA accepts the proposed change, that change
would be imposed uniformly on both generic and brand name
manufacturers. See 57 Fed. Reg. 17950, 17961.

IV

[16] The state law duty to warn by an appropriate label on
the generic ibuprofen drug was not preempted by federal law.
Compliance with both state and federal law was not “impossi-
ble.” Additional warnings would not stand as an obstacle to
the accomplishment of purposes and objectives of Congress.
Perrigo failed to present clear evidence that the FDA would
have rejected the specific hepatotoxicity warnings proposed
by the Gaetas. Accordingly, we REVERSE the district
court’s summary judgment in favor of Perrigo on the ground
of federal preemption.

REVERSED and REMANDED.