United States District Court for the District of Columbia
August 13, 2004.
ALPHAPHARM PTY LIMITED, Plaintiff,
TOMMY G. THOMPSON, Secretary of Health and Human Services, et al., Defendants.
The opinion of the court was delivered by: JAMES ROBERTSON, District Judge
Plaintiff Alphapharm Pty Limited challenges the Food and Drug
Administration's ("FDA") refusal to list the `884 patent for
citalopram (brand name Celexa®) in its Orange Book and FDA's
related refusal to receive Alphapharm's abbreviated new drug
application ("ANDA") for review. Before the Court are the
parties' cross-motions for summary judgment. For the reasons
stated below, defendant's motion must be granted, plaintiff's
cross-motion denied, and the case dismissed.
The Food, Drug, and Cosmetic Act ("FDCA"), 21 U.S.C. § 301 et
seq., prohibits the introduction into interstate commerce of any
new drug unless FDA approves a New Drug Application ("NDA") for
that drug. See 21 U.S.C. § 355(a). An NDA must include "the
patent number and the expiration date of any patent which claims
the drug for which the applicant submitted the application or which claims a method of using such drug and with
respect to which a claim of patent infringement could reasonably
be asserted if a person not licensed by the owner engaged in the
manufacture, use, or sale of the drug." Id. § 355(b)(1); see
also id. § 355(c)(2) (addressing patent information that could
not be submitted before NDA approval). An applicant must amend an
NDA application "[i]f . . . a patent which claims such drug or a
method of using such drug is issued after the filing date but
before approval of the application." Id. § 355(b)(1). If FDA
approves the application, it must publish this information in the
"`Orange Book,' an FDA publication that includes all patent
information that companies have submitted to the agency."
Purepac Pharm. Co. v. Thompson, 354 F.3d 877, 880 (D.C. Cir.
2004); see also 21 U.S.C. § 355(j)(7)(A)(ii) (requiring FDA to
update patent information in the Orange Book every 30 days).
In 1984, Congress enacted the "Hatch-Waxman" amendments to the
FDCA in order to expedite the process by which drug manufacturers
can obtain FDA approval of generic versions of already-approved
brand-name drugs, see Drug Price Competition and Patent Term
Restoration Act of 1984, Pub.L. No. 98-417, 98 Stat. 1585 (1984);
Purepac, 354 F.3d at 879. "[T]he amendments allow companies
seeking such approval to submit Abbreviated New Drug
Applications, known as ANDAs, that `piggyback' on the
safety-and-effectiveness information that the brand-name manufacturers submitted in their NDAs." Purepac, 354 F.3d at
879 (citing 21 U.S.C. § 355(j)(2)(A); 21 C.F.R. § 314.94(a)(3)).
Lest drug innovation be discouraged, the Hatch-Waxman
amendments provide that NDA applicants may obtain exclusivity
periods for innovative drugs. During those exclusivity periods,
FDA may not accept or approve ANDAs for generic versions that
rely for approval on the innovative drug. See
21 U.S.C. § 355(c)(3)(E)(ii)-(iv); id. §§ 355(j)(5)(F)(ii)-(iv). A
five-year exclusivity period is granted to an NDA holder "for a
drug, no active ingredient (including any ester or salt of the
active ingredient) of which has been approved in any other
application under [§ 355(b)]," although an ANDA applicant may
submit an application referencing a listed drug after four years
if the NDA holder of the drug has submitted patent listing
information for the drug pursuant to 21 U.S.C. § 355(b)(1) or
(c)(2). 21 U.S.C. § 355(j)(5)(F)(ii); see also
21 C.F.R. § 314.101(b), (e); 21 C.F.R. § 314.108(b)(2). A six-month extension
of a marketing exclusivity period may be granted for the
submission, at FDA's request, of studies about whether pediatric
use of the new drug will produce health benefits in that
population. See 21 U.S.C. § 355a.
The Hatch-Waxman amendments also "create[d] a strong incentive
for a generic competitor to be the first to file an ANDA and
receive FDA approval: a 180-day period of marketing exclusivity vis-à-vis other generic competitors." Valley Drug
Co. v. Geneva Pharms., Inc., 350 F.3d 1181, 1185 n. 10 (11th
Cir. 2003). "In other words, the first filer to receive FDA
approval is entitled to market the generic versions of the drug
for 180 days without competition from any other generic drug
manufacturers." Id.; see also 21 U.S.C. § 355(j)(5)(B)(iv).
However, "[l]ike NDAs, ANDAs must address patents that cover or
might cover the relevant drugs." Purepac, 354 F.3d at 879. For
each patent, ANDA applicants must file one of four
"certifications" explaining why the ANDA should be approved
despite a patent's claim on the drug: "[A] certification, in the
opinion of the applicant and to the best of his knowledge, with
respect to each patent which claims the listed drug . . . (I)
that such patent information has not been filed, (II) that such
patent has expired, (III) of the date on which such patent will
expire, or (IV) that such patent is invalid or will not be
infringed by the manufacture, use, or sale of the new drug for
which the application is submitted." Id.;
21 U.S.C. § 355(j)(2)(A)(vii)(I)-(IV). (The last certification is known as a
"paragraph IV" certification).
The facts presented by the instant case are these: FDA approved
Forest Laboratories, Inc.'s NDA application for citalopram (under
the brand name of Celexa®) on July 17, 1998. Forest was awarded a
five-year period of marketing exclusivity for an innovative drug under 21 U.S.C. § 355(j)(5)(F)(ii), and a
six-month pediatric exclusivity under 21 U.S.C. § 355a. In its
NDA application, Forest included patent information on three
patents. See Defs.' Mem., at 11. Before its application was
approved, however, Forest sent a letter to FDA discussing the
three patents and amending its application to declare that "there
are no patents which claim the drug or the drug product or which
claim a method of using the drug product and with respect to
which a claim of patent infringement could reasonably be
asserted. . . ." Admin. R., tab 1, at 2.
After the NDA was approved, Forest sent another letter to FDA,
again referencing the three patents mentioned in its application,
but also adding a reference to a fourth the `884 patent. Id.,
tab 2, at 2. This letter concluded with a declaration that "none
of these patents are relevant to [its] approved NDA," and, as
stated in the previous letter, that "there are no patents which
claim the drug or the drug product or which claim a method of
using the drug product and with respect to which a claim of
patent infringement could reasonably be asserted. . . ." Id.
The `884 patent had been issued and assigned to H. Lundbeck A/S
on March 17, 1987. As with NDAs, patents may be extended up to
five years if the patented item was subject to regulatory review
by FDA before the item was marketed. See 67 Fed. Reg. 8,546, 8,546 (Feb. 25, 2002); see also Drug Price
Competition and Patent Term Restoration Act of 1984, Pub.L.
98-417; Generic Animal Drug and Patent Term Restoration Act, Pub.
L. 100-670. In September 1998, Lundbeck filed an application with
the Patent and Trademark Office ("PTO") for a patent term
extension. In response to a request for additional information
from the PTO, Lundbeck stated:
Applicant has demonstrated that the preparation of
the citalopram intermediate . . .; the citalopram
intermediate itself . . .; and the process or
converting the citalopram intermediate to citalopram,
are used in the manufacture of the approved product.
Compl., Ex. C, at 2. The PTO then requested FDA's assistance in
determining the `884 patent's eligibility for an extension. See
67 Fed. Reg. at 8,547. Thereafter, FDA advised the PTO that the
human drug product patented at `884 "had undergone a regulatory
review period and that the approval of Celexa represented the
first permitted commercial marketing or use of the product."
Id. The PTO then requested that FDA determine the product's
regulatory review period, and FDA responded that the applicable
regulatory review period for Celexa is 5,498 days. Id.; Compl.,
Ex. D, at 1. FDA published notice of its findings and, receiving
no objection, informed the PTO that its determination was final.
See Compl., Ex. E.
On December 6, 2002, Alphapharm sent a letter to FDA requesting
that the `884 patent be listed in the Orange Book. See Admin. R., tab 3, at 1. Alphapharm argued that the FDCA
requires an NDA holder to submit to FDA for listing in the Orange
Book "any patent which claims the drug for which the applicant
submitted the application . . . and with respect to which a claim
of patent infringement could reasonably be asserted if a person
not licensed by the owner engaged in the manufacture, use or sale
of the drug," id. (quoting 21 U.S.C. § 355(b)(1)), and that
patent `884 claims the drug citalopram. Alphapharm stated:
The `884 patent was assigned by the inventor . . .
[to] H. Lundbeck A/S, which in turn has licensed the
rights to make, use and sell the drug citalopram
under this patent in the United States to the U.S.
pharmaceutical manufacturer Forest Laboratories, Inc.
. . .
[Lundbeck's] application for an extension of the term
of the `884 patent: (a) constitutes a representation
by the patent owner to the PTO that the `884 patent
claims the drug citalopram; and (b) demonstrates the
patent owner's reliance on this interpretation. . . .
Id., at 2 (emphasis omitted). Alphapharm also attached a letter
from Forest, and said of it that it "constitutes evidence that
Forest, the NDA holder and licensee under the `884 patent,
believes that the `884 patent (a) claims the drug citalopram and
(b) could reasonably be asserted against an unauthorized person
or entity engaged in the manufacture, use or sale of citalopram."
Id. (emphasis omitted). Alphapharm concluded its letter by
stating that "Forest Laboratories should have submitted
statutorily required patent information to FDA for the `884
patent, and has failed to do so." Id. On December 16, 2002, FDA sent a letter to Forest, attaching
Alphapharm's letter and requesting that Forest provide it with
"written confirmation that the challenged data is correct or not
correct pertaining to [its] Celexa NDA," and with "any
corrections that need to be made to the patent and exclusivity
information" relating to listing in the Orange Book. Id., tab
4. Forest responded on January 14, 2002, stating in a letter to
the submission of patent information for Celexa is
accurate, and complies with the requirements of
U.S.C. § 355(b)(1) and 21 C.F.R. § 314.50(h) and §
314.53(b). In addition, all of the information in the
Request for Patent Term Extension for U.S. Patent No.
[`884] is accurate.
U.S. Patent No. [`884] is eligible for Patent Term
Extension pursuant to 35 U.S.C. § 156, but is not eligible
for Orange Book listing (because it claims an
intermediate of citalopram hydrobromide and a method
of its manufacture).
Id., tab 5. FDA forwarded this response to Alphapharm. FDA did
not (and continues not to) list the `884 patent in the Orange
Four and a half years after approval of Forest's NDA, (on
January 17, 2003), Alphapharm submitted an ANDA application for
generic citalopram. The application included a paragraph IV
certification of invalidity and noninfringement of the `884
patent. On March 20, 2003, FDA informed Alphapharm that the
ANDA would not be received for substantive review
pursuant to 21 C.F.R. § 314.101(b)(1), because (a)
the application contained a paragraph IV
certification against the `884 patent which the agency had declined
to include in the Orange Book; and (b) only an ANDA
with a paragraph IV certification against a listed
patent could be received during the [five and a half]
year combined [innovative drug and pediatric]
exclusivity period awarded to this particular
reference listed drug.
Compl., Ex. I, at 3. Thereafter, Alphapharm sent FDA four letters
requesting reconsideration of its decision not to list the `884
patent and not to accept Alphapharm's ANDA. FDA responded on
September 16, 2003, again declining to list the `884 patent or to
receive Alphapharm's ANDA, and stating that, "[u]nless a patent
is listed for Celexa, no applicant may submit an ANDA referencing
that listed drug until the pediatric exclusivity on January 17,
2004," (five and a half years after approval of Forest's NDA).
Admin. R., tab 10, at 3. Plaintiff instituted this action on
November 5, 2003.
Plaintiff complains that FDA's decisions not to list the `884
patent and not to receive Alphapharm's ANDA are arbitrary and
capricious, not in accordance with the Administrative Procedure
Act ("APA"), in excess of statutory authority, and in violation
of the FDCA and related regulations. In reviewing these decisions
of FDA, the first question I must answer is whether the language
of the FDCA is clear and unambiguous. See Chevron U.S.A., Inc.
v. Natural Res. Def. Council, Inc., 467 U.S. 837, 842-43 (1984).
If I answer that question in the affirmative, then the language of the FDCA
controls. See id. But "if the statute is silent or ambiguous
with respect to the specific issue, the question for the court is
whether the agency's answer is based on a permissible
construction of the statute." Id. at 843.
Alphapharm and FDA agree that this case turns on the propriety
of FDA's decision not to list the `884 patent, since FDA may not
receive any ANDA for review that references citalopram during its
five and a half year exclusivity period unless the `884 patent is
listed. Accordingly, I turn directly to the statutory provisions
governing NDA applications and patent listing.
Because the `884 patent was issued long before Forest filed its
NDA for citalopram (approximately ten years),
21 U.S.C. § 335(b)(1) determines Forest's obligations with respect to patents
and FDA's related obligations with respect to listing. This
provision states in relevant part that:
[An NDA] applicant shall file with [its NDA]
application the patent number and the expiration date
of any patent which claims the drug for which the
applicant submitted the application or which claims a
method of using such drug and with respect to which a
claim of patent infringement could reasonably be
asserted if a person not licensed by the owner
engaged in the manufacture, use, or sale of the drug.
If an application is filed under this subsection for
a drug and a patent which claims such drug or a
method of using such drug is issued after the filing
date but before approval of the application, the
applicant shall amend the application to include the
information required by the preceding sentence. Upon
approval of the application, the Secretary shall publish
information submitted under the two preceding
21 U.S.C. § 355(b)(1). The FDCA also provides in relevant part
[t]he Secretary shall, after due notice and
opportunity for hearing to the applicant, withdraw
approval of an application with respect to any drug
under this section if the Secretary finds . . . the
patent information prescribed by subsection (c) of
this section was not filed within thirty days after
the receipt of written notice from the Secretary
specifying the failure to file such information.
Id. § 355(e)(4).
In published regulations, FDA has created a process to resolve
disputes about the propriety of listing or, as is the case here,
the propriety of not listing patents in the Orange Book:
If any person disputes the accuracy or relevance of
patent information submitted to the agency under this
section and published by FDA in the list, or believes
that an applicant has failed to submit required
patent information, that person must first notify the
agency in writing stating the grounds for
disagreement. . . . The agency will then request of
the applicable new drug application holder that the
correctness of the patent information or omission of
patent information be confirmed. Unless the
application holder withdraws or amends its patent
information in response to FDA's request, the agency
will not change the patent information in the list.
If the new drug application holder does not change
the patent information submitted to FDA, a 505(b)(2)
application or an abbreviated new drug application
under section 505(j) of the act submitted for a drug
that is claimed by a patent for which information has
been submitted must, despite any disagreement as to the correctness of the patent
information, contain an appropriate certification for
each listed patent.
21 C.F.R. § 314.53(f). These regulations commit the resolution of
disputes between ANDA applicants and patent holders regarding the
validity or correctness of the listed patent information to
actions between ANDA applicants and patent holders, rather than
to FDA action.*fn1
See 59 Fed. Reg. 50,338, 50,348 (Oct.
3, 1994); see also 35 U.S.C. § 271.
FDA asserts that the Court's Chevron inquiry can end at step
one, because this language of the FDCA is clear and unambiguous.
FDA argues that the FDCA delegates to it only "a ministerial duty
to list patents," that "FDA is not required to determine
independently whether a patent meets the statutory criteria for
listing," and that FDA may not list a patent unless the NDA
applicant submits the patent information for listing. Defs.'
Mem., at 16-17. Forest having certified that there are no patents
relevant to its NDA, FDA says refusal to list the `884 patent in
the Orange Book was consistent with its purely ministerial duty.
Alphapharm submits that "FDA's `ministerial role' approach to its duty regarding patent listings is an
impermissible interpretation [of the Hatch Waxman amendments]
. . ., and renders 21 U.S.C. § 355(e)(4) meaningless and
superfluous." Pl.'s Mem., at 23. It argues that §§ 355(b)(1) and
(e)(4) must be read together, and that they require FDA it take
appropriate (i.e. substantive) action to determine whether a
patent belongs in the Orange Book.
On its face, § 355(b)(1) prescribes apparently ministerial
duties, and nothing in § (b)(1) itself suggests that it is
limited by § (e)(4) or any other subsection. Section (e)(4),
however, is limited by another subsection subsection (c).
21 U.S.C. § 355(e)(4) ("The Secretary shall, after due notice and
opportunity for hearing to the applicant, withdraw approval of an
application with respect to any drug under this section if the
Secretary finds . . . the patent information prescribed by
subsection (c) of this section was not filed within thirty days
after receipt of written notice from the Secretary specifying the
failure to file such information." (emphasis added)). Subsection
(c) prescribes the filing of patent information described in
subsection (b) that "could not be filed with the submission of an
application under subsection (b) of this section because the
application was filed before the patent information was required
under subsection (b) of this section or a patent was issued after
the application was approved under such subsection." Id. § 355(c)(2). In other words, subsection (c)
addresses patent information that either post-dates the effective
date of the Hatch-Waxman amendments, or patent information that
comes into existence after approval of an NDA. This is not the
same patent information mentioned in subsection (b)(1), which
includes patent information that exists at the time of and is
filed with the submission of an NDA, or patent information
concerning a patent issued after the filing date but before
approval of an NDA application.*fn2 These provisions are
clear and unambiguous, and they support FDA's "ministerial role"
Even if there were enough ambiguity in these provisions to move
to Chevron step two, FDA's reading of its duties regarding
patent listings is the most natural one. This Court will "set
aside an FDA decision only if it is `arbitrary, capricious, an
abuse of discretion, or otherwise not in accordance with law.'"
Purepac, 354 F.3d at 883 (quoting 5 U.S.C. § 706(2)(A)). "FDA
interpretations of the FDCA receive deference, as do its interpretations of its own regulations."
Id. (internal citations omitted).
The Federal Circuit recently observed that FDA's
"interpretation of the [Hatch-Waxman] Act set forth in
21 C.F.R. § 314.53(f) is a reasonable one: that the Act does not require it
to police the listing process by analyzing whether the patents
listed by NDA applicants actually claim the subject drugs or
applicable methods of using those drugs." Apotex, Inc. v.
Thompson, 347 F.3d 1335, 1349 (Fed. Cir. 2003).*fn3 This
reading is consistent with FDA's claim, first announced shortly
after the enactment of the Hatch-Waxman amendments, that it "has
no expertise in the field of patents," and, therefore, "no basis
for determining whether a use patent covers the use sought by the
generic applicant." 54 Fed. Reg. 28,872, 28,909 (Jul. 10, 1989); see also, e.g., aaiPharma, 296 F.3d at 241 ("[T]he FDA's
reading of the statute is reasonable in light of the division of
intellectual labor established by the Hatch-Waxman Act. FDA
points out that the whole point of the Act's paragraph IV
certification scheme is to let private parties sort out their
respective intellectual property rights through patent
infringement suits while FDA focuses on its primary task of
ensuring that drugs are safe and effective. This division of
labor is appropriate because FDA has no expertise in making
patent law judgments.").
As the Fourth Circuit explained (in reviewing the "ministerial
role" theory in the context of a § (c)(2), § (d)(6),*fn4 and
§ (e)(4) challenge), another reading would vastly expand the
patent listing role of FDA:
There can be no question that the FDA's reading . . .
is reasonable. Indeed, [the] requirement that the FDA
"shall file" the patent information submitted by NDA
holders is most naturally read to suggest that
Congress intended for the FDA to play a purely
ministerial role. . . .
According to [plaintiff, the FDA is obligated] to
independently determine whether the NDA applicant has listed all the patents that meet the statutory
criteria for Orange Book listing. We conclude,
however, that the statute can reasonably be read to
impose only a much more limited duty on the
FDA. . . . [T]he FDA's duty is not to ensure the
correctness of the list of patents submitted for
Orange Book listing, but simply to ensure that either
a patent list has been filed or a declaration has
been made that there are no patents to be
listed. . . . If . . . subsection (d)(6) commands the
FDA to second guess the NDA applicant's judgments
about which patents claim its drug, that command is
not limited to cases in which a third party has
questioned the correctness of those judgments. . . .
[I]t would require the FDA to "screen the universe of
patents to determine which ones should be listed[.]"
. . . We conclude that on the better reading of
subsection (d)(6), the FDA is required only to ensure
that each NDA applicant has submitted either a list of patents
claiming its drug or a declaration that there are no
patents to be listed.
aaiPharma, 296 F.3d at 238-40 (internal citations
Moreover, the D.C. Circuit has questioned
whether FDA could look behind an NDA holder's request to list or
delist a patent. See Am. Bioscience, Inc. v. Thompson,
269 F.3d 1077, 1085 (D.C. Cir. 2001) ("Indeed, it is not at all clear
to us that FDA, under its regulations, would be authorized to reject the obvious intent of
an NDA holder even if it acted directly contrary to a court
I find FDA's acceptance of nothing more than a "ministerial
role" in patent listing to be reasonable, a permissible
construction of the FDCA, and neither arbitrary or capricious.
Indeed, under Alphapharm's theory, subsections (b)(1) and (e)(4)
would require FDA to vastly expand its activities with respect to
patent listing. Alphapharm has not pointed to anything to
indicate that Congress intended such a role for FDA and I find
that the statute does not do so. The policy issues implicated by
Forest's behavior and Alphapharm's frustration are interesting,
but they are not for me to resolve and should be raised with
Because I have found FDA's decision not to list the `884 patent
reasonable, it follows that FDA properly refused to receive
Alphapharm's ANDA application. See Pl.'s Mem., at 21 ("The
FDA's ruling of September 16, 2003 refused to accept Alphapharm's
ANDA for citalopram as of its January, 2003 submission date
solely because it contained a paragraph IV certification for the `884 patent, which FDA has refused to list
in the Orange Book. Consequently, both of FDA's refusals hinge on
its refusal to list).