Otsuka Pharmaceutical Co., Ltd. et al v. Burwell et al

Filing 118

MEMORANDUM OPINION. Signed by Judge George Jarrod Hazel on 5/27/2015. (jf2s, Deputy Clerk)

IN THE UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF MARYLAND
Southern Division
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OTSUKA PHARMACEUTICAL CO., LTD.,
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Plaintiff,

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v.

Case No.: GJH-15-852
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SYLVIA MATHEWS BURWELL, ET AL.,
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Defendants.
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MEMORANDUM OPINION
This is an action brought by Plaintiffs Otsuka America Pharmaceutical, Inc., Otsuka
Pharmaceutical Development and Commercialization, Inc., and Otsuka America Pharmaceutical
Inc. (collectively, “Otsuka”) pursuant to the Administrative Procedure Act (“APA”), 5 U.S.C. §
701, et seq., challenging various actions taken by Defendant Food and Drug Administration
(“FDA”).1 Specifically, Otsuka challenges FDA’s approval of the sale of four generic versions of
the prescription brand drug aripiprazole, which is marketed and sold under the brand name
of Abilify® by Otsuka. After the Court denied Otsuka’s motion for temporary restraining order
and/or preliminary injunction on April 29, 2015 (see ECF No. 100), FDA, Otsuka, and the
Defendant-Intervenors2 filed cross-motions for summary judgment. See ECF Nos. 107-09. On
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In addition to naming FDA as a defendant, Otsuka has also named Sylvia Mathews Burwell,
Secretary of the U.S. Department of Health and Human Services, and Drs. Margaret Hamburg
and Stephen Ostroff as defendants. Because the allegations against these four defendants are the
same, the Court will refer to them collectively as the “FDA.”
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Defendant-Intervenors include Apotex Inc., Apotex Corp., Teva Pharmaceuticals USA, Inc.,
Alembic Pharmaceuticals Ltd., Alembic Ltd., Alembic Global Holdings S.A., Alembic
Pharmaceuticals, Inc., Zydus Pharmaceuticals (USA) Inc., Torrent Pharma Inc., Torrent
Pharmaceuticals Ltd., and Sandoz, Inc.

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May 20, 2015, the Court held a hearing on these fully briefed motions. For the reasons discussed
more fully below, the Court will DENY Otsuka’s motion for summary judgment, and will
GRANT FDA’s and Defendant-Intervenors’ motions for summary judgment.
I.

BACKGROUND
This case involves the interplay between statutory exclusivities, particularly orphan drug

exclusivity, statutory and regulatory mandates that require labels of generic drugs to contain the
same information as their brand counterpart, and requirements that pediatric information be
included on drug labels. Specifically, Otsuka, the new drug application holder for Abilify®,
contends that, as a result of FDA’s recent approval of a pediatric indication for Abilify® that is
protected by orphan drug exclusivity, FDA is precluded from approving generic versions of
Abilify® until its orphan drug exclusivity expires in December 2021 because 21 U.S.C. §
355a(o) does not permit this type of pediatric information to be omitted from a generic’s label.3
A.

Statutory and Regulatory Framework
1.

New Drug Applications and Supplemental New Drug Applications

Under the FDCA, pharmaceutical companies seeking to market the initial version of a
drug (also known as the “innovator” or “pioneer” drug) must first obtain FDA approval by filing
a new drug application (“NDA”) containing extensive scientific data demonstrating the safety
and effectiveness of the drug. See 21 U.S.C. § 355(a), (d). A sponsor may thereafter submit a
supplemental new drug application (“sNDA”) seeking FDA’s approval of a new indication of an
already approved drug. See 21 C.F.R. § 314.70(b). Drug sponsors must justify the labeling
change proposed in the supplement by submitting data supporting the safety and effectiveness of
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In its April 29, 2015 Memorandum Opinion, the Court referred to 21 U.S.C. § 355a(o) as
section 505A(o), which is a reference to the corresponding section of the Federal Food, Drug,
and Cosmetic Act (“FDCA”). For purposes of this Memorandum Opinion, the Court will use the
citation from the United States Code.

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the drug for the new indication. See 21 U.S.C. § 355(a) and (d); see also 21 C.F.R. §
314.70(b)(3)(iv)-(v). FDA will refuse to approve the sNDA if, among other reasons, the
sponsor’s investigations do not show that the drug is safe or effective for “the conditions of use
prescribed, recommended, or suggested in the proposed labeling.” 21 U.S.C. § 355(d)(1), (2),
(5).
2.

Abbreviated New Drug Applications

The Drug Price Competition and Patent Term Restoration Act of 1984 (the HatchWaxman Amendments), codified at 21 U.S.C. § 355 and 35 U.S.C. §§ 156, 271, & 282, permits
a drug manufacturer to submit an abbreviated new drug application (“ANDA”) requesting
approval of a generic version of an already approved drug product. See 21 U.S.C. § 355(j).
ANDA applicants need not submit clinical data to demonstrate the safety and efficacy of the
generic product, as with an NDA. See id. Rather, an ANDA relies on FDA’s previous findings
that the product approved under the NDA is safe and effective. Among other information, an
ANDA must include data showing that the generic drug product is bioequivalent to the innovator
product. See 21 U.S.C. § 355(j)(2)(A)(iv), (j)(4)(F); see also 21 C.F.R. § 314.127(a)(6)(i),
314.94(a)(7).
3.

Orphan Drug Exclusivity

To justify the costly and risky investment of time and money in preparing and submitting
NDAs and sNDAs, Congress has provided these applicants with certain periods of statutory
exclusivity during which they can sell their product without generic competition. One of these
periods of statutory exclusivity is found in the Orphan Drug Act provisions of the FDCA, Pub. L.
97-414, 96 Stat. 2049. There, Congress encouraged drug manufacturers to develop drugs for the
treatment of rare diseases or disorders affecting small patient populations. One of the incentives

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that Congress provided in the Orphan Drug Act is a seven-year period of market exclusivity for
approved orphan drugs. See 21 U.S.C. § 360cc(a). FDA’s regulations provide that, when a drug
receives orphan exclusivity, “no approval will be given to a subsequent sponsor of the same drug
for the same use or indication for 7 years.” 21 C.F.R. § 316.3(b)(12).
4.

Labeling Requirements

FDA has promulgated regulations requiring certain pediatric information to be included
on a prescription drug’s label.4 For example, in the “Indications and Usage” section of the Full
Prescribing Information portion, “[i]f evidence is available to support the safety and
effectiveness of the drug or biological product only in selected subgroups of the larger
population (e.g., . . . patients in a special age group) . . . a succinct description of the limitations
or usefulness of the drug and any uncertainty about anticipated clinical benefits,” must be
included. 21 C.F.R. § 201.57(c)(2)(i)(B) (emphasis added). Elsewhere the regulations explain
that, “[i]f there is a specific pediatric indication different from those approved for adults that is
supported by adequate and well-controlled studies in the pediatric population, it must be
described under the ‘Indications and Usage’ section.” § 201.57(c)(9)(iv)(B).
Likewise, the “Dosage and Administration” section “must state the recommended dose
and, as appropriate,” among other things, “[d]osages for each indication and subpopulation.” §
201.57(c)(3)(C) (emphasis added). This section must include appropriate pediatric dosage
information “[i]f there is a specific pediatric indication different from those approved for adults
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A drug’s labeling includes “all labels and other written, printed, or graphic matter upon any
article or any of its containers or wrappers, or accompanying such article.” 21 U.S.C. §
321(m)(1)-(2). The labeling must “contain [a]dequate information for such use, including
indications, effects, dosages, routes, methods, and frequency and duration of administration and
any relevant warnings, hazards, contraindications, side effects, and precautions, under which
practitioners licensed by law to administer the drug can use the drug safely and for the purposes
for which it is intended, including all conditions for which it is advertised or represented.” 21
C.F.R. § 201.100(d)(1).
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that is supported by adequate and well-controlled studies in the pediatric population.” §
201.57(c)(9)(iv)(B).
The regulations require that the labeling also includes other specific pediatric
information. Where a specific pediatric indication has been demonstrated by adequate and wellcontrolled studies, the pediatric use section “must cite any limitations on the pediatric
indication,” among other things. Id. “If there are specific statements on pediatric use of the drug
for an indication also approved for adults that are based on adequate and well-controlled studies
in the pediatric population, they must be summarized in the ‘Pediatric use’ subsection . . . .” §
201.57(c)(9)(iv)(C).
5.

The “Same Labeling” Requirement

Generally, generic drugs must contain the same information on their labels as the label of
their respective brand-name predicate drug. See 21 U.S.C. § 355(j)(2)(A)(v), (j)(4)(G); 21 C.F.R.
§ 314.94(a)(8)(iv). Nonetheless, there are situations where ANDA applicants may carve out from
proposed labeling patent or exclusivity-protected conditions of use and obtain approval for the
remaining non-protected conditions of use. For example, the FDCA allows for exceptions if “the
new [ANDA] drug and the listed drug are produced or distributed by different manufacturers.”
21 U.S.C. § 355(j)(2)(A)(v); see also 21 C.F.R. §§ 314.94(a)(8)(iv), 314.92(a)(1), 314.127(a)(7).
In such cases, ANDA applicants may, for example, carve out indications protected by patent or
exclusivity in certain circumstances.
Additionally, Congress enacted 21 U.S.C. § 355a(o) which identifies certain situations
where the FDA cannot deny approval based on the omission of pediatric information on a
brand’s label from the generic’s label. Section 355a(o) provides:
A drug for which an application has been submitted or approved
under section 355(j) of this title shall not be considered ineligible

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for approval under that section or misbranded under section 352 of
this title on the basis that the labeling of the drug omits a pediatric
indication or any other aspect of labeling pertaining to pediatric
use when the omitted indication or other aspect is protected by
patent or by three-year exclusivity under [21 U.S.C. §
355(j)(5)(F)(iii) or (iv)].
21 U.S.C. § 355a(o)(1). According to Otsuka, “the statute defines FDA’s approval authority by
expressly limiting the agency’s authority to disapprove a generic drug based on specific pediatric
labeling omissions.” ECF No. 107 at 20.5 Because the only labeling omissions the statute allows
are for pediatric indications or information pertaining to pediatric use protected by patent or by
three-year exclusivity under § 355(j)(5)(F), Otsuka argues that FDA cannot omit pediatric
labeling information that is protected by orphan drug exclusivity. See id. at 19-20. FDA, on the
other hand, contends that section 355a(o) “does not limit [its] authority to carve-out pediatric
labeling where a carve-out would otherwise be appropriate”; instead, section 355a(o) “provides
FDA with additional authority to retain Hatch-Waxman-protected pediatric information in
ANDA labeling where a carve-out would not be appropriate (because such information is
necessary for safe use of the product).” ECF No. 109 at 15 (citing Administrative Record
(“AR”) 498).
B.

Case-Specific Background

Otsuka is the NDA holder for Abilify®. See AR 1010-31. FDA first approved Abilify®
on November 15, 2002, then for schizophrenia, and FDA has since approved it for schizophrenia
in adolescents, acute treatment of manic and mixed episodes associated with Bipolar I Disorder
in both adult and pediatric patients, irritability associated with autistic disorder in pediatric
patients, and as an add-on treatment for depression in adults. See id. In 2005, Otsuka submitted

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For the citations to page numbers in this Memorandum Opinion, the Court uses the page
numbers assigned to the document from CM/ECF or PACER.

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an application to FDA requesting orphan drug designation for Abilify® “for the treatment of
Tourette Syndrome in children and adolescents.” ECF No. 77-2 at ¶ 10.
In 2006, FDA granted Otsuka orphan drug designation for the use of Abilify® for the
treatment of Tourette’s Disorder. See id. at ¶ 11. This designation meant, among other things,
that Otsuka would be entitled to a seven-year period of market exclusivity running from the date
of FDA’s approval of the use of Abilify® for the treatment of Tourette’s Disorder. See id.
During that seven-year period, FDA would be precluded from approving a drug for the same use
or indication. Id. When the FDA awarded Abilify® orphan designation for the treatment of
Tourette’s Disorder, no sNDA had been submitted and no safety and efficacy studies had been
conducted in any population group. As such, Otsuka initiated clinical trials which ultimately
demonstrated the safety and efficacy of Abilify® to treat Tourette’s Disorder in the pediatric
population. See id. at ¶¶ 14-15, 24. Following the conclusion of these trials, Otsuka submitted a
sNDA to FDA seeking approval for the new indication of the treatment of Tourette’s Disorder in
pediatric patients. See id. at ¶ 16. FDA ultimately approved Otsuka’s sNDA for Abilify® for
treatment of Tourette’s Disorder in the pediatric population. See AR 468-69. As a result of
FDA’s decision, Otsuka obtained approval for a pediatric Tourette’s Disorder indication for
Abilify® that is protected by orphan drug exclusivity.
Otsuka contends that by receiving this pediatric approval, which is protected by orphan
drug exclusivity, it is entitled to a seven-year period of total market exclusivity (until December
2021). During that time, Otsuka argues that the law precludes FDA from approving any generic
version of Abilify® for any of its FDA-approved indications (absent a license from Otsuka). It is
against this backdrop that Otsuka filed a complaint, along with a motion for a temporary
restraining order and/or preliminary injunction, against FDA seeking to stay the effect of FDA’s

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approvals of generic versions of Abilify® that occurred on April 28, 2015, to prevent FDA from
issuing any further approvals prior to the expiration of Otsuka’s seven year period of orphan
drug exclusivity, and to prohibit the recipients of generic approvals from distributing their
respective versions of generic Abilify®.
Specifically, on April 28, 2015, FDA issued a letter decision to Otsuka setting forth its
determination that ANDA applicants seeking to market generic versions of Abilify could carveout from their labeling the Tourette’s Disorder indication and related information. See AR 488502. FDA determined that, contrary to Otsuka’s contentions, section 355a(o) did not prohibit a
labeling carve-out for the Tourette’s Disorder indication. See id. FDA based its determination on
an in-depth analysis of the relevant statutory provisions, regulations, past agency precedent, and
case-law. See AR 490- 502. FDA also concluded, based on its scientific review, that “omission
of the protected Tourette’s Disorder indication and related information does not render the
generic drug less safe or effective than Abilify for the remaining non-protected conditions of
use” and, thus, “permitted [] ANDAs to omit from their labeling all information related to
treatment of Tourette’s Disorder.” AR 502. As such, FDA approved four generic version of
Abilify®. See AR 502; see also AR 643-45; AR 660-62; AR 678-80; AR 696-98; AR 714-16;
AR 733-35; AR 750-52. All of these generic versions carved out protected labeling relating to
Tourette’s Disorder in pediatric patients. See id.
Just hours after FDA’s approval, the Court held a hearing on April 28, 2015 to address
Otsuka’s motion for temporary restraining order and/or preliminary injunction. See ECF No. 94.
The following day, the Court issued its Memorandum Opinion and accompanying Order denying
Otsuka’s motion (“April 29 Opinion”). See ECF Nos. 100 & 101. After the Court set an
expedited briefing schedule, Otsuka, FDA, and Defendant-Intervenors all filed cross-motions for

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summary judgment on May 11, 2015. See ECF Nos. 107-109. A hearing on the cross-motions
was held on May 20, 2015. Having considered the arguments of the parties, the Court will deny
Otsuka’s motion for summary judgment and grant the FDA’s and Defendant-Intervenors’
motions for summary judgment.
II.

STANDARD OF REVIEW
Under Fed.R.Civ.P. 56(a), summary judgment is appropriate when the pleadings and the

evidence demonstrate that “there is no genuine dispute as to any material fact and the movant is
entitled to judgment as a matter of law.” Fed.R.Civ.P. 56(a). In a case involving review of a final
agency action under the APA, however, the standard set forth in Rule 56(a) does not apply
because of the limited role of a court in reviewing the administrative record. See Roberts v.
United States, 883 F.Supp.2d 56, 62-63 (D.D.C. Mar. 23, 2012); see also Kaiser Found. Hosps.
v. Sebelius, 828 F.Supp.2d 193, 197-98 (D.D.C. 2011). Summary judgment thus serves as a
mechanism for deciding, as a matter of law, whether the agency action is supported by the
administrative record and is otherwise consistent with the APA standard of review. See Richard
v. INS, 554 F.2d 1173, 1177 & n. 28 (D.C. Cir. 1977). Thus, “the function of the district court is
to determine whether or not as a matter of law the evidence in the administrative record
permitted the agency to make the decision it did.” Kaiser Found. Hosps., 828 F.Supp .2d at 198
(internal quotations and citations omitted).
Under the APA, the Court shall “hold unlawful and set aside agency action, findings and
conclusions” that are “arbitrary, capricious, an abuse of discretion, or otherwise not in
accordance with law.” 5 U.S.C. § 706(2)(A). In evaluating agency decision making under the
APA, the Court’s only role is to determine whether “the decision was based on a consideration of
the relevant factors and whether there has been a clear error of judgment.” Citizens of Overton

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Park v. Volpe, 401 U.S. 402, 416 (1971), abrogated on other grounds, Califano v. Sanders, 430
U.S. 99 (1977). The scope of review “under the ‘arbitrary and capricious’ standard is narrow and
a court is not to substitute its judgment for that of the agency.” Motor Vehicle Mfrs. Ass’n v.
State Farm Mut. Auto. Ins. Co., 463 U.S. 29, 42-43 (1983). Furthermore, administrative actions
are presumed valid; thus, a “court will not second guess an agency decision or question whether
the decision made was the best one.” C & W Fish Co. v. Fox, 931 F.2d 1556, 1565 (D.C. Cir.
1991). The APA only requires the Court to decide whether the agency “articulated a rational
connection between the facts found and the choice made.” Baltimore Gas & Elec. Co. v. Natural
Res. Def. Council, 462 U.S. 87, 105 (1983) (citations omitted).
III.

DISCUSSION
Otsuka claims that 21 U.S.C. § 355a(o) directly addresses the question of when generics

can omit from their labels the pediatric information that is included in the brand’s label. See ECF
No. 107 at 15. According to Otsuka, section 355a(o) permits FDA to approve generic drugs that
omit pediatric labeling in only two circumstances – (1) when that information is protected by
patent; and (2) when that information is protected by three-year new clinical study exclusivity.
Section 355a(o) does not, according to Otsuka, allow for the omission of labeling information
protected by pediatric orphan drug exclusivity. See id at 19. By approving Otsuka’s sNDA for
Abilify® to treat Tourette’s Disorder in pediatric patients – an indication which is indisputably
covered by orphan drug exclusivity – Otsuka argues that FDA was precluded from approving an
ANDA for a generic version of Abilify® for any of its approved indications because section
355a(o) does not allow for the omission of this type of pediatric information from the generic’s
label. Thus, when FDA did approve generic versions of Abilify® on April 28, 2015, Otsuka
argues it did so in contravention of section 355a(o). FDA and Defendant-Intervenors, on the

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other hand, contend that while section 355a(o) limits FDA’s ability to deny approvals in two
specified circumstances, it does not limit its ability to grant approvals in others. The Court must
therefore address the scope of 21 U.S.C. § 355a(o).
A.

Applicable Level of Deference

Ordinarily, a court reviews “an agency’s construction of the statute which it administers”
under the familiar two-step process of Chevron, U.S.A., Inc. v. Natural Resources Defense
Council, Inc., 467 U.S. 837, 842 (1984). Despite arguing in its motion for temporary restraining
order and/or preliminary injunction that the two-step Chevron process was, in fact, the
appropriate analysis, Otsuka now contends (for the first time) that Skidmore deference – a less
stringent form of deference – applies. See Skidmore v. Swift & Co., 323 U.S. 134 (1944); see also
Christensen v. Harris County, 529 U.S. 576, 587 (2000) (“Interpretations such as those in
opinion letters – like interpretations contained in policy statements, agency manuals, and
enforcement guidelines, all of which lack the force of law – do not warrant Chevron like
deference.”).6 According to Otsuka, Chevron deference is not appropriate here because FDA’s
interpretation was not the subject of notice and comment rulemaking. See ECF No. 107 at 16-18.
The Court disagrees.
The Supreme Court has made clear that “‘[t]he want of’ notice and comment ‘does not
decide’” whether Chevron applies. Barnhart v. Walton, 535 U.S. 212, 222 (2002) (quoting
United States v. Mead Corp., 533 U.S. 218, 230-31 (2001)). The relevant question is whether “it
is ‘apparent from the agency’s generally conferred authority and other statutory circumstances

Under Skidmore deference, an agency interpretation “receives weight in proportion to its
‘power to persuade,’ as measured by factors like ‘the thoroughness evident in its consideration,
the validity of its reasoning, [and] its consistency with earlier and later pronouncements.’”
Shipbuilders Council of Am., Inc. v. U.S. Dep’t of Homeland Security, 673 F. Supp. 2d 438, 453
(E.D. Va. 2009).
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that Congress would expect the agency to be able to speak with the force of law when it
addresses ambiguity in the statute or fills a space in the enacted law.’” Patel v. Napolitano, 706
F.3d 370, 376 (4th Cir. 2013) (quoting Mead, 533 U.S. at 229)). Several factors are relevant to
resolving the issue, including “the interstitial nature of the legal question, the related expertise of
the Agency, the importance of the question to administration of the statute, the complexity of
that administration, and the careful consideration the Agency has given the question over a long
period of time.” Barnhart, 535 U.S. at 222.
As Defendant-Intervenors rightly point out, Courts applying these factors have routinely
held that FDA letter decisions like the one at issue here are entitled to Chevron deference. For
example, in Mylan Labs., Inc. v. Thompson, 389 F.3d 1272 (D.C. Cir. 2004), the D.C. Circuit
rejected the argument that FDA’s interpretation of the pediatric exclusivity provision contained
in 21 U.S.C. § 355a was not entitled to deference because it was “expressed in letters to the
parties” rather than in a regulation. 389 F.3d at 1279. Given “the complexity of the statutory
regime under which the FDA operates, the FDA’s expertise [and] the careful craft of the scheme
it devised to reconcile the various statutory provisions” and that “FDA’s decision made no great
legal leap but relied in large part on its previous determination of the same or similar issues,” the
D.C. Circuit concluded that Chevron deference was appropriate. Id. at 1280.
Likewise, in AstraZeneca Pharm. LP v. FDA, 713 F.3d 1134 (D.C. Cir. 2013), the D.C.
Circuit applied Chevron deference under circumstances similar to those presented here. In that
case, AstraZeneca filed suit against FDA seeking an injunction to prevent the agency from
approving ANDAs that AstraZeneca claimed were barred by a change to its labeling (the
addition of a table) that was protected by pediatric exclusivity. See id. at 1136. The district court
dismissed AstraZeneca’s initial suit as unripe because FDA had not yet decided whether to

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approve any ANDAs with the new labeling. See id. at 1137. Four days later, FDA approved
ANDAs with the new labeling and “issued a letter to AstraZeneca on the same day explaining its
decision that [the table] was not entitled to a period of exclusivity.” Id. The district court granted
summary judgment to FDA, concluding that the statute was “ambiguous” and that FDA’s
interpretation in its letter decision was “reasonable.” Id. at 1138. In affirming the district court’s
decision under the two-step Chevron test, the D.C. Circuit specifically recognized that Chevron
deference applied to “FDA decision letters.” Id. at 1139.
The Court sees no reason to depart from the approach taken by the D.C. Circuit in Mylan
Labs and AstraZeneca, especially given the complexity of the statutory regime at issue, FDA’s
expertise in regards to this complex scheme, and the fact that FDA’s decision on the scope of
Otsuka’s exclusivity under the FDCA was based on its longstanding understanding of its general
carve-out authority (embodied in several regulations) and its precedent addressing the specific
question of whether to approve ANDAs that carve out pediatric information protected by orphan
drug exclusivity. See AR 499-500; see also Mylan Labs., Inc., 389 F.3d 1280. While Otsuka
correctly observes that these cases are not binding on this Court, decisions from the D.C. Circuit
“are afforded particular weight in the area of administrative law.” Ohio Valley Envt’l Coal. v.
U.S. Army Corps of Eng’rs, 674 F. Supp. 2d 783, 800 (S.D. W. Va. 2009). Furthermore, the only
case involving the FDA cited by Otsuka to support the notion that Skidmore deference applies
was United States v. Undetermined Quantities of Articles of Drug, 145 F. Supp. 2d 692 (D. Md.
2001), which predated the Supreme Court’s decisions of Mead and Barnhard, and, in any event,
involved a non-binding FDA policy statement that lacked the force of law. The Court therefore
concludes that the appropriate level of deference afforded to FDA in this case is that provided by
the two-step Chevron framework.

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B.

Chevron—Step One7

Having decided that Chevron deference applies here, the Court begins with the first step
of the analysis which asks whether “Congress has directly spoken to the precise question at
issue,” such that “the intent of Congress is clear.” Nat’l Elec. Mfrs. Ass’n v. Dept. of Energy, 654
F.3d 496, 504 (4th Cir. 2011) (quoting Chevron, 467 U.S. at 842-43). If the intent of Congress is
clear, “that is the end of the matter; for the court, as well as the agency, must give effect to the
unambiguously expressed intent of Congress.” Chevron, 467 U.S. at 842-43. If, however, “the
statute is silent or ambiguous with respect to the specific issue,” id. at 843, Congress has not
spoken clearly, and a permissible agency interpretation of the statute merits judicial deference.
Thus, “[t]he objective of Chevron step one is not to interpret and apply the statute to resolve a
claim, but to determine whether Congress’s intent in enacting it was so clear as to foreclose any
other interpretation.” King v. Burwell, No. 14-1158, 2014 WL 3582800, at *5 (4th Cir. July 22,
2014) (citing Grapevine Imports, Ltd. v. United States, 636 F.3d 1368, 1377 (Fed. Cir. 2011)).
Under the first step of Chevron, “a reviewing court is to ‘employ [ ] traditional tools of
statutory construction’ to determine whether Congress addressed ‘the precise question at issue.’”
Nat. Elec. Mfrs. Ass’n., 654 F.3d at 504 (quoting Chevron, 467 U.S. at 842, 843 n. 9). Courts,
therefore, begin this analysis with the text and structure of the statute. Id. (citing Cabell
Huntington Hosp. Inc. v. Shalala, 101 F.3d 984, 986 (4th Cir. 1996)). After all, “the plain
language of the statute” is “the most reliable indicator of Congressional intent.” Schafer v.

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In its April 29 Opinion addressing Otsuka’s motion for temporary restraining order and/or
preliminary injunction, the Court discussed, at length, Otsuka’s likelihood of success on the
merits. See Otsuka Pharm. Co. v. Burwell, No. 15-852, 2015 WL 1962240, at *5-10 (D. Md.
Apr. 29, 2015). Because much of that discussion is relevant for present purposes, the
forthcoming discussion of the two-step Chevron analysis involves some repetition from the
Court’s prior opinion. This opinion, however, also addresses new and additional arguments not
previously discussed by the Court in its April 29 Opinion.

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Astrue, 641 F.3d 49, 54 (4th Cir. 2011). Additionally, the Fourth Circuit has “described
legislative history as one of the traditional tools of interpretation to be consulted at Chevron’s
step one.” Nat. Elec. Mfrs. Ass’n., 654 F.3d at 504–05 (citing Elm Grove Coal Co. v. Dir., O.
W.C.P., 480 F.3d 278, 293-94 (4th Cir. 2007)).
Thus, the Court begins its Chevron step one inquiry into Congress’s intent, as it must,
from “the fundamental canon that statutory interpretation begins with the language of the statute
itself.” Butler v. West, 164 F.3d 634, 639 (D.C. Cir. 1999). Here, as mentioned, the relevant
statute is 21 U.S.C. § 355a(o). Specifically, section 355a(o) provides, “[a] drug for which an
application has been submitted or approved under section 355(j) of this title shall not be
considered ineligible for approval under that section or misbranded under section 352 of this title
on the basis that the labeling of the drug omits a pediatric indication or any other aspect of
labeling pertaining to pediatric use when the omitted indication or other aspect is protected by
patent or by three-year exclusivity under [Section 505(j)(5)(F)(iii) or (iv)].” 21 U.S.C. §
355a(o)(1).
According to Otsuka, this language “directly [speaks] to the precise question of when
pediatric indications and other information pertaining to pediatric use may be omitted from a
generic’s label.” ECF No. 107 at 19. Specifically, Otsuka contends that, by enacting section
355a(o), “Congress provided that only pediatric labeling protected by patent and three-year new
clinical studies exclusivity could be omitted from a generic’s label.” Id. Because the statute does
not expressly permit pediatric labeling protected by orphan drug exclusivity to be omitted from a
generic label, FDA cannot, according to Otsuka, “approv[e] a generic drug that omits [] pediatric
labeling protected by orphan drug exclusivity.” Id. To do so, would, according to Otsuka,
“require[] adding text to the statute.” Id. at 23.

15

As this Court held in its April 29 Opinion, in reaching this conclusion, “Otsuka ignores
the critical fact that section [355a(o)] sets forth circumstances where FDA cannot deny approval
for a labeling carve-out; it does not, as Otsuka contends, address situations where FDA can or
cannot grant approval.” Otsuka Pharm. Co., No. 15-852, 2015 WL 1962240, at *7 (emphasis in
original). Otsuka argues that this is a mere “linguistic distinction,” and that because Congress
used a double negative when it used the phrase “shall not be considered ineligible for approval,”
the correct interpretation of this phrase is “FDA shall approve.” ECF No. 107 at 20-22. But in
making this argument, Otsuka is attempting to change or add text to the statute. The Court will
not follow Otsuka’s lead. See 62 Cases, More or Less, Each Containing Six Jars of Jam v.
United States, 340 U.S. 593, 596 (1951) (“[O]ur problem is to construe what Congress has
written. After all, Congress expresses its purpose by words. It is for us to ascertain – neither to
add nor to subtract, neither to delete nor to distort.”); United States v. Sonmez, 777 F.3d 684, 688
(4th Cir. 2015) (“We will not construe the statute in such a manner, because we are required to
interpret statutory language as written and are not permitted to add words of our own
choosing.”). Regardless, neither the actual text of the statute nor Otsuka’s suggested alternative
tells FDA when it may not approve an ANDA. To do so, the text would need to be further
rewritten to say “FDA shall only approve ANDAs with omitted pediatric indications if” or “FDA
may not approve ANDAs with omitted pediatric indications unless.”
To be clear, other provisions in the FDCA demonstrate that Congress knew how to
specifically and affirmatively direct FDA’s ability to approve an ANDA when it wanted to do so.
For example, in section 355(j)(4), the FDCA provides that, “subject to Paragraph (5)”, the FDA
“shall approve an [ANDA] unless . . .” barred by one of a list of grounds for disapproval. Unlike
section 355a(o), therefore, section 355(j)(4) directs a specific action unless a specified bar to that

16

action exists. By contrast, section 355a(o) merely tells FDA it may not disapprove an ANDA
based on the omission of pediatric indications that is the result of patent or three-year new
clinical study exclusivity with no language to indicate that it intended to restrict FDA’s ability to
approve ANDAs not covered by those two categories. 8 If Congress intended to limit FDA’s
approval authority, it could have done so explicitly using language similar to what it used in
355(j)(4). See Jama v. Immigration and Customs Enforcement, 543 U.S. 335, 341(2005) (“We
do not lightly assume that Congress has omitted from its adopted text requirements that it
nonetheless intends to apply, and our reluctance is even greater when Congress has shown
elsewhere in the same statute that it knows how to make such a requirement manifest”). Otsuka
cannot therefore turn a provision limiting FDA’s disapproval authority into a provision limiting
its approval authority.
Furthermore, although Otsuka goes to great lengths to try to distance itself from the
expressio unius est exclusio alterius canon (the expression of one thing is the exclusion of
another) upon which it previously relied when seeking a temporary restraining order and/or
preliminary injunction, Otsuka’s arguments remain fundamentally the same. See ECF No. 107 at
23-27 (arguing “The Text Only Refers To Patent Protection And Three-Year Exclusivity”).
Indeed, Otsuka’s reliance not on what the text of section 355a(o) includes, but on the
significance of what it omits is, in effect, just a repackaged version of the same arguments
previously rejected by this Court. Those arguments are no more persuasive now.

Additionally, as FDA points out, Otsuka incorrectly reverses the language of “shall not be
considered ineligible for approval” into “FDA shall approve.” ECF No. 112 at 11-12. A correct
reversal (which itself would be a departure from the statute’s plain language) would read: “shall
be considered eligible for approval.” (emphasis added). By removing the words “considered
eligible” in its variation of the phrase, Otsuka has entirely eliminated the critical concept of
eligibility. Just because something must be considered qualified to be chosen does not mandate
that it will actually be chosen. See id.
8

17

The Supreme Court has “long held that the expressio unius canon does not apply ‘unless
it is fair to suppose that Congress considered the unnamed possibility and meant to say no to it,’
and that the canon can be overcome by ‘contrary indications that adopting a particular rule or
statute was probably not meant to signal any exclusion.’” Marx v. Gen. Revenue Corp., 133 S.
Ct. 1166, 1175 (2013) (internal citations omitted); see also Barnhart v. Peabody Coal Co., 537
U.S. 149, 168 (2003) (“We do not read the enumeration of one case to exclude another unless it
is fair to suppose that Congress considered the unnamed possibility and meant to say no to it.”).
Initially, Otsuka cited no evidence, and conceded there was no evidence found, that
Congress even contemplated orphan drug exclusivity at the time section 355a(o) was proposed
and enacted, much less that Congress expressly considered orphan drug exclusivity and
purposefully excluded it. See ECF No. 99 at 17:8-15.
In its subsequent motion for summary judgment, however, Otsuka identified specific
legislative history that, it contends, demonstrates that the Senate Health, Education, Labor, and
Pension (“HELP”) Committee was “considering orphan drug issues, and orphan drug
exclusivity, specifically” when it “work[ed] on a predecessor bill” prior to the enactment of
section 355a(o). ECF No. 77 at 9, 43. As Defendant-Intervenors correctly point out, however,
Otsuka provides no evidence that the Senate HELP Committee ever discussed the implications of
orphan drug exclusivity as it relates to section 355a(o). See ECF No. 108 at 17-19. Simply
showing that some members of the Congress that enacted section 355a(o) were generally aware
of the Orphan Drug Act or orphan drug issues hardly suggests that by not mentioning orphan
drugs in section 355a(o) Congress intended, by negative implication, to limit FDA’s existing
carve-out authority under 21 U.S.C. §§ 355(j) and 360cc.

18

Thus, in the absence of evidence suggesting that Congress contemplated orphan drug
exclusivity when it enacted section 355a(o), Otsuka cannot rely on the expressio unius canon, or
similar arguments, to turn section 355a(o) into a restriction on FDA’s carve-out authority. See
e.g., Barnhart, 537 U.S. at 170 (“The enunciation of two exceptions does not imply an exclusion
of a third unless there is reason to think the third was at least considered.”); Clinchfield Coal Co.
v. Fed. Mine Safety & Health Review Comm’n, 895 F.2d 773, 779 (D.C. Cir. 1990) (“The drafter
(here Congress) may simply not have been focusing on the point in the second context; and,
where an agency is empowered to administer the statute, Congress may have meant that in the
second context the choice should be up to the agency.”); Greene v. United States, 79 F.3d 1348,
1355 (2d Cir.1996) (“The ancient maxim expressio unius est exclusio alterius . . . cautions us
against engrafting an additional exception to what is an already complex [statutory scheme].”).
The background and reasoning behind the passage of section 355a(o) further refutes
Otsuka’s interpretation of the provision. As a starting point, all parties agree that section 355a(o)
was crafted to address the so-called “Glucophage loophole.” See ECF Nos. 107 at 31-35, 108-1
at 33-36, 109-1 at 14-15. A discussion of the background of the Glucophage loophole is,
therefore, useful.
Bristol Myers Squibb, Glucophage’s sponsor, undertook pediatric studies of the drug,
which already had an indication approved in adults, and earned three years of new clinical study
exclusivity for a pediatric indication. As a result, FDA would not approve any ANDAs for
Glucophage, even for the adult indication, until the three-year period of exclusivity resulting
from its pediatric indication expired because the drug was approved for the same indication in
adults making protected pediatric information necessary for the safe use of the drug. See AR
480-81 n. 24 (citing 147 CONG. REC. H10209). FDA’s concern stemmed from its regulations

19

which stated that “if there are specific statements on pediatric use of the drug for an indication
also approved for adults that are based on adequate and well-controlled studies in the pediatric
population, they must be summarized in the ‘Pediatric use’ subsection.” 21 CFR
201.57(c)(9)(iv)(C) (emphasis added).9 The result was de facto exclusivity for all populations
and the prevention of generic products from reaching consumers.
Aware of the potential adverse consequences to consumers, Congress added section
355a(o) “to override the [existing] requirement that generic versions of pioneer drugs bear
labeling for pediatric indications.” 147 CONG. REC. H10210 (memorandum to the United States
Congress Re: Proposed Amendment to the Hatch-Waxman Act (H.R. 2887), referring to the
proposal as the “Anti-Glucophage Bill”). Representative John Dingell, the ranking minority
member of the relevant House committee, expressly noted that the misuse of pediatric
information to garner three-year exclusivity for a certain indication and wholly block generic
competition for all approved indications is “a fundamental abuse of the system and were the
FDA . . . to accept the claim, consumers would be harmed.” 147 CONG. REC. H8105.
Representative Dingell also noted that the provision that eventually became section 355a(o)
“closes this potential loophole by instructing the FDA to approve generic drugs without
proprietary pediatric labeling awarded to product sponsors under the Hatch-Waxman Act.” Id;
see also 147 CONG. REC. H10212 (same); accord id. at H10210 (statement of Rep. Eshoo)
(“Importantly the bill we will vote on today . . . closes the ‘Glucophage loophole’ which allowed

Otsuka points to other regulations as being the “relevant provisions,” (see ECF No. 113 at 6),
but those provisions contain similar language. See 21 C.F.R. § 201.80(f)(9)(ii) (“if there is a
specific pediatric indication (i.e., an indication different from those approved for adults) that is
supported by adequate and well-controlled studies in the pediatric population, it shall be
described under the ‘Indications and Usage’ section of the labeling and appropriate pediatric
dosage information shall be given under the ‘Dosage and Administration’ section of the
labeling.”) (emphasis added).
9

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one company to get an additional 3 years of marketing exclusivity. This bill ensures that no
company will be able to take advantage of the exclusivity granted by this very important
legislation.”).
Given this context, it would defy logic to believe that in enacting this measure to prevent
a three-year exclusivity from becoming a “fundamental abuse of the system” that harmed
consumers, Congress nonetheless intended to permit the seven-year exclusivity Otsuka seeks
here. The Court concludes that it did not. 10 Otsuka also contends that the failure of section
355a(o) to address orphan drug issues means that the existing regulations foreclose approval here
for the same reason that the FDA would not approve ANDAs for generic Glucophage. Again, the
Court disagrees. The FDA’s concern in Glucophage was that an unprotected adult indication
existed while the corresponding pediatric indication was protected and would need to be carvedout. As stated by the FDA, “when a product is approved for use in adults for an indication that
also occurs in pediatric populations, FDA generally presumes, based on experience, that the
product will be used in the pediatric population for that adult-approved indication regardless of
whether it is labeled for that use.” AR 479-80. Therefore, in some of those cases, “a carve-out of
pediatric information while adult information is retained in the ANDA labeling may result in a
potential safety risk to pediatric patients.” AR 497. Abilify® does not have an adult indication
10

Defendant-Intervenors are correct to point out that the number of pediatric patients who suffer
from Tourette’s disorder (and therefore qualified Otsuka to receive orphan drug exclusivity for
that indication) is fewer than 120,000. See ECF No. 77-2 at ¶ 10. Even if Abilify® were
prescribed to this entire pediatric population, those sales still would be only a small percentage of
the more than $4.7 billion worth of Abilify® sales in the United States in fiscal year 2013. See
Otsuka Holdings Co., Ltd., Fact Book: Supplementary Materials, Financial Results FY 2014, 6
(2014), available at http://www.otsuka.com/en/financial/pdf.php?financial=338.at 11. Thus, as
Defendant-Intervenors put it: “Otsuka seeks to block the approval and marketing of generic
aripiprazole products for all uses when its orphan drug exclusivity by its own admission could at
the very most cover fewer than 120,000 patients. This . . . would destroy the careful balance
Congress struck when it enacted the Orphan Drug Act and the Hatch-Waxman Amendments to
the FDCA.” ECF No. 108 at 35.
21

for Tourette’s syndrome. See ECF No. 77-2 at ¶ 7. Hence, the FDA’s concerns with, and
regulations applying to, the Glucophage problem do not exist here.
In sum, when the Court considers the text of section 355a(o), as well as its legislative
history, the Court cannot conclude that section 355a(o) clearly proscribes FDA’s ability to omit
from a generic’s label information pertaining to pediatric orphan drug exclusivity. Thus, if the
Court’s role here was simply to “interpret and apply the statute to resolve a claim,” the Court
would, without further analysis, side with the interpretation of FDA and Defendant-Intervenors.
See Chevron, 467 U.S. at 842. However, given 355a(o)’s silence on orphan drug exclusivity, the
Court cannot find that Congress’s intent in enacting 355a(o), as it relates to its impact on orphan
drugs, if any, is so clear as to completely foreclose Otsuka’s interpretation. The Court must
therefore proceed to Chevron step two.
C.

Chevron—Step Two

Finding that Congress has not “directly spoken to the precise question at issue,” the Court
moves to Chevron’s second step. Chevron, 467 U.S. at 842. At step two, the Court asks whether
the “agency’s [action] is based on a permissible construction of the statute.” Id. The Court may
overturn the FDA’s interpretation under Chevron step two only if the statute “unambiguously
foreclosed the agency’s statutory interpretation.” Catawba Cnty., N.C. v. E.P.A., 571 F.3d 20, 35
(D.C. Cir. 2009). Thus, the Court will not “usurp an agency’s interpretive authority by
supplanting its construction with our own, so long as the interpretation is not ‘arbitrary,
capricious, or manifestly contrary to the statute.’” Philip Morris USA, Inc. v. Vilsack, 736 F.3d
284, 290 (4th Cir. 2013) (quoting Chevron, 467 U.S. at 844, 845). “A construction meets this
standard if it ‘represents a reasonable accommodation of conflicting policies that were
committed to the agency’s care by the statute.’” Id. Courts have been clear that “[r]eview under

22

this standard is highly deferential, with a presumption in favor of finding the agency action
valid.” Ohio Vall. Envt’l Coalition v. Aracoma Coal Co., 556 F.3d 177, 192 (4th Cir. 2009).
Moreover, an agency’s construction of its own regulations is entitled to “substantial
deference,” Thomas Jefferson Univ. v. Shalala, 512 U.S. 504, 512 (1994), and is accorded
“controlling weight unless it is plainly erroneous or inconsistent with the regulation.” Id. Broad
deference to an agency is especially appropriate where, as here, “a complex and highly technical
regulatory program” is concerned, requiring “significant expertise” and the “exercise of
judgment grounded in policy concerns.” Id. (citing Pauley v. BethEnergy Mines, Inc., 501 U.S.
680, 697 (1991)).
Under the FDCA, FDA has broad authority to approve ANDAs carving out exclusivities,
including orphan drug exclusivity. That authority does not appear to be abrogated by section
355a(o), which, by its terms, constrains FDA’s authority to refrain from approving an ANDA,
instead of, as Otsuka urges, constraining its authority to approve ANDAs. While it is generally
true that generic drugs must contain the same information on their labels as the label of their
respective brand-name pioneer drug, this principle does not require a generic drug’s labeling to
be identical to that of the listed drug it references in every respect. Instead, the same labeling
rules contained in the Hatch-Waxman Amendments “reflect Congress’s intent that the generic
drug be safe and effective for each condition of use prescribed, recommended, or suggested in
the generic drug labeling but do not require that an ANDA be approved for each condition of use
for which the listed drug is approved.” AR 478. Indeed, the legislative history of these
amendments demonstrates Congress’s desire to permit ANDA applicants to carve out from their
labels otherwise protected information. Specifically, Congress acknowledged that “[t]he bill
permits an ANDA to be approved for less than all of the indications for which the listed drug has

23

been approved. . . . [T]he applicant need not seek approval for all of the indications for which the
listed drug has been approved.” H.R. REP. NO. 98-857(I), at 21 (1984).
The Orphan Drug Act further confirms FDA’s authority to approve ANDAs carving out
an orphan drug exclusivity. Specifically, 21 U.S.C. § 360cc(a) provides that “for a drug
designated under section 360bb of this title for a rare disease or condition, the Secretary may not
approve another application under section 355 of this title . . . for such drug for such disease or
condition . . . until the expiration of seven years from the date of the approval of the approved
application” (emphasis added). Interpreting this language in Sigma-Tau Pharms., Inc. v. Schwetz,
288 F.3d 141 (4th Cir. 2002), the Fourth Circuit opined:
By using the words ‘such drug for such disease or condition,’
Congress made clear its intention that [section 360cc] was to be
disease-specific, not drug-specific. In other words, the statute as
written protects uses, not drugs for any and all uses. Congress
could have written [section 360cc] more broadly by prescribing
that the FDA ‘may not approve another application . . . for such
drug,’ but it chose not to draft the statute in that way.
Id. at 145. As such, the Fourth Circuit upheld the right of an ANDA to carve out an indication
protected by orphan drug exclusivity as a permissible difference between the generic’s label and
the pioneer’s label due to a difference in manufacturer. See also Bristol Myers Squibb v. Shalala,
91 F.3d 1493, 1500 (D.C. Cir. 1996) (recognizing that the Orphan Drug Act “expresses the
legislature’s concern that the new generic be safe and effective for each indication that will
appear on its label; whether the label for the new generic lists every indication approved for use
of the pioneer is a matter of indifference”).

24

Moreover, the interpretation Otsuka seeks is directly contrary to FDA’s prior decisions
on orphan drug exclusivity carve-outs where that exclusivity incorporated pediatric information.
In fact, FDA has, on multiple occasions over the past decade, approved ANDA drug products
during the NDA-holder’s seven-year period of orphan drug exclusivity, despite the fact that the
orphan indication covered a pediatric use. See AR 482-83; see also ECF No. 82 at 27-28.
Because “FDA has been consistent in how it has interpreted” the carve-out provisions over an
extended period of time, the deference afforded to FDA’s interpretation of its statute is
particularly high. Hospira, Inc. v. Burwell, No.14-02662, 2014 WL 4406901, at *13 (D. Md.
Sept. 5, 2014); see also Kasten v. Saint-Gobain Performance Plastics Corp., 131 S. Ct. 1325,
1336 (2011) (noting that the “length of the time the agencies have held” their position “suggests
that [the position] reflect[s] careful consideration” and is entitled to deference). The Court
therefore finds FDA’s interpretation of the statute to be permissible.
Otsuka, however, contends that FDA’s decision to approve ANDAs to market generic
versions of Abilify® for uses that are not protected by orphan drug exclusivity was
impermissible insofar as it violates FDA’s own pediatric labeling regulation, known as the
Physician Labeling Rule which spells out certain general requirements for labeling in pediatric
populations. See 21 C.F.R. § 201.57; see also ECF No. 107 at 45-46. Specifically, Otsuka argues
that FDA’s Physician Labeling Rule “require[s] all prescription drugs to contain pediatric
labeling” and specifies that drugs without the labeling “would be considered misbranded.” ECF
No.107 at 46. Accordingly, Otsuka maintains that the Physician Labeling Rule should have
blocked FDA’s approval of ANDAs for generic versions of Abilify® because “FDA’s general
carve-out authority is limited by the agency’s binding pediatric labeling regulation.” Id. This
case, however, is not about the general requirements for pediatric information in labeling; rather,

25

this case is about FDA’s statutory authority to approve ANDAs that carve out an entire protected
orphan pediatric indication, a permissible practice which the Physician Labeling Rule does not
change. See 71 Fed. Reg. 3925, 3963 (Jan. 24, 2006) (“This [Physician Labeling] rule does not
change the requirement to exclude any condition of use or indication from the labeling of a
generic product when necessary (e.g., when the reference listed drug has patent protection or
market exclusivity for an indication), nor does it prevent, as described at § 314.127(a)(7),
approval of an ANDA when the reference listed drug has protected labeling.”).11 The Court,
therefore, does not believe the Physician Labeling Rule limits FDA’s general carve-out authority.
Furthermore, to the extent that Otsuka argues that the state of the law prior to section
355a(o)’s passage was that ANDAs could not be approved through a carve out of a pediatric
indication protected by orphan drug exclusivity, and that the statute’s silence on orphan drug
exclusivity indicates FDA cannot now approve ANDAs without running afoul of its regulations,
it is, in effect, challenging FDA’s interpretation of its own regulations. At the hearing, Otsuka
avoided acknowledging this position and for good reason. An agency’s interpretation of its own
regulations is “controlling unless plainly erroneous or inconsistent with the regulation.” Auer v.
Robbins, 519 U.S. 452, 461 (1997). It cannot be said that FDA’s interpretation of its regulations
here were plainly erroneous or inconsistent with the Physician Labeling Rule.
Indeed, FDA’s regulations demonstrate the authority granted by the FDCA to permit
labeling changes based on the “omission of an indication or other aspect of labeling protected by
patent or accorded exclusivity under [the FDCA].” 21 C.F.R. § 314.94(a)(8)(iv). The regulations
11

The Court recognizes that FDA has acknowledged that this language was not present when this
regulation was originally enacted in 1994. See ECF No. 117. To the extent the Court was
interested in that distinction at the hearing, it was for the purpose of determining Congress’s
intent in passing section 355a(o), which occurred prior to the preamble’s inclusion in 2006. The
Court has made its determination regarding section 355a(o) but finds this passage relevant in
addressing the regulation as it exists now.

26

permit FDA to approve an ANDA that omits “aspects of the listed drug’s labeling [that] are
protected by patent, or by exclusivity [if] such differences do not render the proposed drug
product less safe or effective than the listed drug for all remaining, nonprotected conditions of
use.” 21 C.F.R. § 314.127(a)(7). Additionally, section 314.94(a)(8)(iv) of the regulations also
sets forth specific examples of permissible differences in labeling that may result because the
generic drug product and listed drug product are produced or distributed by different
manufacturers. These differences include “differences in expiration date, formulation,
bioavailability, or pharmacokinetics, labeling revisions made to comply with current FDA
labeling guidelines or other guidance, or omission of an indication or other aspect of labeling
protected by patent or accorded exclusivity under section 505(j)(5)(F) of the act.” 21 C.F.R. §
314.94(a)(8)(iv) (emphasis added).
The Court therefore finds that the FDCA, its legislative history, the case law, and FDA’s
regulations all support the FDA’s construction of the statute that allows it to carve out an
indication or other information from ANDA labeling when that indication or information is
protected by orphan drug exclusivity as long as the ANDA with that carved out label remains
safe and effective for the remaining non-protected conditions of use. To be sure, Otsuka’s
reading of section 355a(o) would nullify the limitation expressly written into section 360cc – that
the exclusivity is given to a drug “for [the orphan] disease or condition” – and instead treat the
orphan drug exclusivity as extending to the drug for any and all diseases and conditions, directly
contradicting that provision’s text and the Fourth Circuit’s holding in Sigma-Tau. If that was
Congress’s intent, it is certainly left unclear by the statute and FDA’s interpretation is
reasonable.

27

IV.

CONCLUSION
For the reasons stated above, the Court will DENY Otsuka’s motion for summary

judgment and will GRANT FDA’s and Defendant-Intervenors’ motions for summary judgment.

Dated: May 27, 2015

/S/
George J. Hazel
United States District Judge

28