VIROPHARMA INCORPORATED v. HAMBURG et al

Filing 65

MEMORANDUM AND OPINION. Signed by Judge Ellen S. Huvelle on 1/9/13. (lcesh1)

UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF COLUMBIA

ViroPharma, Inc.,
Plaintiff,
v.
Margaret A. Hamburg, M.D., in her official
capacity as Commissioner, Food and Drug
Administration, et al.,
Civil Action No. 12-0584 (ESH)
Defendants,
and
Akorn, Inc., et al.,
Intervenor-Defendants.

MEMORANDUM OPINION
ViroPharma, Inc. manufactures the antibiotic Vancocin®. On April 13, 2012,
ViroPharma sued Margaret Hamburg, in her official capacity as the Commissioner of the Food
and Drug Administration; Kathleen Sebelius, in her official capacity as the Secretary of the
Department of Health and Human Services; and the agencies themselves (collectively, the
“FDA”) to challenge the FDA’s approval, on April 9, 2012, of three Abbreviated New Drug
Applications (“ANDAs”) permitting the marketing of generic versions of Vancocin (vancomycin
hydrochloride capsules or “vancomycin”). (See Complaint (Apr. 13, 2012) [ECF No. 1]
(“Compl.”).) ViroPharma alleges that the FDA approved the three ANDAs (1) in violation of
ViroPharma’s statutory right under the Federal Food, Drug, and Cosmetic Act (“FFDCA”), 21
U.S.C. §§ 301 et seq., to a three-year period of exclusivity for Vancocin, extending through
December 15, 2014; and (2) based solely on in vitro (laboratory) bioequivalence testing in
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violation of the FDA’s own regulations requiring in vivo (human) bioequivalence testing. (Id. ¶
2.) The Court will refer to these as ViroPharma’s “statutory exclusivity claim” (see id. ¶¶ 75–78
(Count II)) and its “bioequivalence claim.” (See id. ¶¶ 69–74 (Count I).) The three generic
manufacturers whose vancomycin ANDAs were approved – Akorn, Inc., Alvogen, Inc., and
Watson Laboratories, Inc. – have also joined the suit as intervenor-defendants.
On April 23, 2012, this Court denied ViroPharma’s motion for a preliminary injunction
to require the FDA to withdraw its approval of the three vancomycin ANDAs and to refuse to
approve any additional vancomycin ANDAs until ViroPharma’s claims were adjudicated on the
merits. See ViroPharma Inc. v. Hamburg, No. 12-584, 2012 WL 1388183 (D.D.C. Apr. 23,
2012) (“Memorandum Opinion”). Now seeking adjudication on the merits, ViroPharma has
filed a motion for summary judgment (see Plaintiff’s Motion for Summary Judgment (July 20,
2012) [ECF No. 51] (“Pl. Mot.”)), urging the Court to reconsider its arguments “with the benefit
of the additional elaboration herein and additional time to consider the law and arguments.” (Id.
at 10.) Defendants have also filed a motion to dismiss, or, in the alternative, for summary
judgment (see Federal Defendants’ Motion to Dismiss or, in the Alternative, for Summary
Judgment (Sept. 4, 2012) [ECF No. 53] (“Def. Mot.”)), and intervenor-defendants have likewise
filed a motion to dismiss, or, in the alternative, for summary judgment. (See IntervenorDefendants’ Motion to Dismiss, or, in the Alternative, for Summary Judgment (Sept. 4, 2012)
[ECF No. 56] (“Inter.-Def. Mot.”).)
ViroPharma is correct that a court’s determinations regarding a motion for preliminary
relief are not considered to be the law of the case. (See Pl. Mot. at 9 (quoting Belbacha v. Bush,
520 F.3d 452, 458 (D.C. Cir. 2008) and citing Kuzinich v. Cnty. of Santa Clara, 689 F.2d 1345,
1350-51 (9th Cir. 1982) and Nat’l Football League Players Ass’n v. Pro-Football, Inc., 857 F.

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Supp. 71, 79 (D.D.C. 1994).)) However, nothing in the parties’ submissions convinces the Court
to reach a different conclusion today. ViroPharma all but admits that it has presented no
substantially new arguments, but rather it relies on “additional elaboration” (Pl. Mot. at 10), none
of which persuades the Court to reverse itself. Moreover, no new facts have been presented that
would dictate a different result. Although the parties have submitted additional excerpts from
the administrative record, which the Court has reviewed, these submissions do not alter the
Court’s judgment. To the extent that any portion of the supplemented record affects the Court’s
opinion, it serves only to bolster it. (See, e.g., Memo from Lorenz re: Consult Response on
ViroPharma December 22, 2011 Submission (Apr. 9, 2012), Part H to Joint Appendix,
FDA004629-4637 (outlining reasons that data from Genzyme trial was not “essential to
approval” of Vancocin sNDA and subsequent labeling changes)). Therefore, the Court
incorporates by reference the conclusions that it reached in its prior Memorandum Opinion, and
will limit its discussion to the few additional points that are arguably being raised for the first
time.
BACKGROUND
The Court assumes familiarity with the relevant statutory and procedural background,
which was described in great detail in the Court’s Memorandum Opinion. In the briefest terms,
ViroPharma states a statutory exclusivity claim based on QI Program Supplemental Funding Act
of 2008, Pub. L. No. 110-379, 122 Stat. 4075 (the “QI Act”). That Act amended the FFDCA to
render “Old Antibiotics,” including Vancocin, eligible for three-year market exclusivity for
changes approved on the basis of “new clinical investigations (other than bioavailability studies)
. . . conducted or sponsored by the person submitting the [sNDA].” 21 U.S.C. § 355(j)(5)(F)(iv).
ViroPharma made certain changes to the labeling of Vancocin, and on this basis, it sought three-

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year exclusivity. The FDA denied ViroPharma’s request in accordance with its interpretation of
21 U.S.C. § 355(v)(3)(B), which provides that exclusivity is not available for “any condition of
use for which the [Old Antibiotic] . . . was approved before the date of the enactment [of the QI
Act].” In the FDA’s view, “the labeling changes related to and refined the already-approved
indication for treatment of [Clostridium difficile], and included a dosing regimen that was
encompassed within, and at most refined, the prior regimen.” (Def. Mot. at 9-10.) In short, the
new labeling pertained only to previously-approved conditions of use and thus, under §
355(v)(3)(B), was excluded from exclusivity. ViroPharma has challenged the FDA’s
interpretation and application of § 355(v)(3)(B) and the administrative actions taken based
thereon – specifically, the denial of exclusivity to ViroPharma, and the approval of ANDAs for
three generic versions of Vancocin.
ViroPharma also states a bioequivalence claim, arguing that the FDA violated its own
regulations when it approved generic copies of Vancocin based on in vitro rather than in vivo
testing. ViroPharma alleges that the FDA’s regulations establish a default requirement that in
vivo testing must be submitted to demonstrate that a generic drug is “bioequivalent” to the
original, pioneer drug. (See Pl. Mot. at 21-22.) The FDA counters that there is no such default
rule; on the contrary, the agency retains the discretion to determine the appropriate method for
demonstrating the bioequivalence of a given drug on a case-by-case basis. (See Def. Mot. at 3435.) In this instance, the FDA concluded that in vitro dissolution tests were “the most accurate,
sensitive, and reproducible approach for demonstrating bioequivalence” for vancomycin. (Id. at
33.)

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ANALYSIS
I.

LEGAL STANDARDS
A. Motion for Summary Judgment
Normally, a motion for summary judgment under Rule 56 shall be granted if “the

pleadings, depositions, answers to interrogatories, . . . admissions on file, . . . [and] affidavits . . .
show that there is no genuine issue as to any material fact and that the moving party is entitled to
judgment as a matter of law.” Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 247 (1986)
(quoting Fed. R. Civ. P. 56(c)). “In a case involving review of a final agency action under the
[APA], however, the standard set forth in Rule 56(c) does not apply because of the limited role
of a court in reviewing the administrative record.” Sierra Club v. Mainella, 459 F. Supp. 2d 76,
89 (D.D.C. 2006) (citation omitted). Under the APA, it is the role of the agency to resolve
factual issues to arrive at a decision that is supported by the administrative record, whereas “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.” Id. at 90 (quoting
Occidental Eng’g Co. v. INS, 753 F.2d 766, 769-70 (9th Cir. 1985)).
B. Standard of Review
The Court begins “with the first step of the two-part framework announced in Chevron . .
. and asks[s] whether Congress has ‘directly addressed the precise question at issue.’” Mayo
Found. for Med. Educ. & Research v. United States, 131 S. Ct. 704, 711 (2011) (quoting
Chevron, U.S.A., Inc. v. Natural Res. Def. Council, 467 U.S. 837, 842-843 (1984)). If the
statutory language in 21 U.S.C. § 355(v)(3)(B) is unambiguous and “the intent of Congress is
clear, that is the end of the matter; for the [C]ourt, as well as the agency, must give effect to the
unambiguously expressed intent of Congress.” Chevron, 467 U.S. at 842–43. However, “if the

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statute is silent or ambiguous with respect to the specific issue,” the Court will proceed to step
two of the Chevron analysis and ask whether the FDA’s interpretation is “permissible.” Id. at
843. At this step, the interpretation is “given controlling weight unless” it is “manifestly
contrary to the statute.” Id. at 844. As the D.C. Circuit recently reaffirmed, “[t]he Chevron step
two question . . . is not whether the [plaintiff’s] proposed alternative is an acceptable policy
option but whether the [agency action] reflects a reasonable interpretation of [the statute].
Coalition for Common Sense in Gov’t Procurement v. United States, No. 11-535, slip op. at 12
(D.C. Cir. Jan. 4, 2013).
II.

VIROPHARMA’S STATUTORY EXCLUSIVITY CLAIM
This Court extensively analyzed ViroPharma’s statutory exclusivity claim in its prior

Memorandum Opinion, concluding that the claim would likely fail on the merits. In its summary
judgment motion, ViroPharma has added a single alternative justification in addition to
rehashing the same arguments that the Court has already rejected – ViroPharma suggests that
“[i]f the labeling changes approved in the Vancocin sNDA constituted previously approved
conditions of use, then the structure of innovator drug regulation under the FDCA would be
seriously compromised.” (Pl. Mot. at 20.) ViroPharma claims that if the FDA’s logic is applied,
as ViroPharma interprets it, manufacturers could make labeling changes without prior FDA
approval because the changes would be considered “previously approved.” (Id.) And although
the statute requires that generic drug labels reflect the same “previously approved” “conditions
of use” as the innovator drug label, ViroPharma asserts that the FDA’s logic would also lead to
the unacceptable conclusion that “generic vancomycin manufacturers could have – before the
Vancocin sNDA was approved – adopted the labeling changes included therein on their own
accord.” (Pl. Mot. at 20-21 (emphasis in original).)

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ViroPharma seriously misconstrues the FDA’s position. The FDA does not claim that the
labeling changes were “previously approved.” Rather, “the conditions of use for the drug – how,
to whom, and for what purpose the drug is administered – were previously approved.” (Def.
Mot. at 27 (emphasis added).) The FDA has been very clear, from its response to ViroPharma’s
Citizen Petition through its briefing of the present motions, that it considered the new Vancocin
labeling to have “merely refined and added new details to describe the previously approved
conditions of use.” (Id. (emphasis added).) The FDA has used the same definition of “condition
of use” in applying subsection (v)(3)(B) that it has used in applying other subsections of the
statute, such as subsection (j)(2)(A)(i), which requires ANDAs to have the same conditions of
use as the innovator. (See id.)
As the Court explained at length in its prior Memorandum Opinion, the agency acted
within its discretion to determine that “the revision of the Vancocin label to incorporate clinical
data that supports and refines labeling regarding already approved conditions of use, does not
constitute approval for a condition of use that has not been ‘approved before the enactment’
within the meaning of section 505(v)(3)(B).” (CP Resp. at 71; see also Memorandum Opinion at
30.) The Court reaffirms this conclusion here, especially given the “high level of deference,”
Serono Labs. v. Shalala, 158 F.3d 1313, 1320 (D.C. Cir. 1998) (internal quotation marks and
citation omitted), accorded to the agency where the agency’s decision “involve[s] a subject
matter [that] is technical, complex, and dynamic,” Nat’l Cable & Telecomms. Ass’n v. Brand X
Internet Servs., 545 U.S. 967, 1002–03 (2005) (internal quotation marks and citation omitted;
some alterations in the original), and “rests on the ‘agency’s evaluations of scientific data within
its area of expertise,’” Serono Labs., 158 F.3d at 1320 (quoting A.L. Pharma, Inc. v. Shalala, 62

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F.3d 1484, 1490 (D.C. Cir. 1995); citing Schering Corp. v. FDA, 51 F.3d 390, 399–400 (3rd Cir.
1995)).
Notably, ViroPharma’s argument that its labeling changes reflect a new dosing regimen
and thus a new “condition of use” conflicts with its own prior treatment of its sNDA.
ViroPharma never previously suggested that the sNDA presented a new indication, dosing
regimen, or route of administration. (See Inter.-Def. Mot. at 12.) Significantly, if ViroPharma
had considered its sNDA as presenting a new condition of use, it “would have been required to
conduct an assessment under the Pediatric Research Equity Act, P.L. 108-155 (“PREA”).” Id.
“PREA requires that for certain applications, including sNDAs, for a new active ingredient, new
indication, new dosage form, new dosing regimen or new route of administration, the applicant
must conduct pediatric studies unless a waiver or deferral has been obtained.” (Id. at 12-13
(citing 21 U.S.C. § 355C(a).) ViroPharma did not submit any PREA assessments and did not
seek a waiver or deferral of such requirements. (Id. at 13 (citing CP Resp. at 72.)) Furthermore,
FDA’s approval letter to ViroPharma explicitly stated that none of the PREA criteria applied and
ViroPharma never objected to that conclusion. (Id. at 13 (citing Approval Letter for Supplement
28 with Approved Labeling (Dec. 14, 2011), Part P of Joint Appendix, at FDA005129).)
The FDA made this very point in its opposition to ViroPharma’s preliminary injunction
motion (see Federal Defendants’ Memorandum in Opposition to Plaintiff’s Motion for
Temporary Restraining Order and/or Preliminary Injunction (April 17, 20120) [ECF No. 22], at
27-28) and in its briefing of the instant motion. (See Fed. Mot. at 29-30). Intervenor-defendants
have also cited this omission by ViroPharma. (See Inter.-Def. Mot. at 12-13). ViroPharma’s
silence in response is deafening. ViroPharma’s failure to conduct pediatric studies certainly
further bolsters the Court’s conclusion that the new labeling did not constitute or reflect new

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conditions of use, nor did ViroPharma consider it as such until it was expedient to do so in the
course of this litigation.
The Court also notes that the additional portions of the administrative record that have
now been submitted reveal that the Genzyme studies upon which ViroPharma based its
exclusivity claim were not essential to the approval of changes in the label. (See Inter.-Def. Mot.
at 20.) For example, one internal FDA memorandum concluded,
This dosing regimen is neither a new dose (i.e. outside of the range of the
currently approved dose) nor a regimen for a new condition. The “125 mg
administered 4 times daily” dose of vancomycin has been adopted as the
“standard dose” since the 1980’s . . . Although the Genzyme study uses the lower
dose of 125 mg four times daily . . . it does not compare different dosing
regiments of vancomycin . . . . The Genzyme studies do support the previous
findings that the lower dose is an effective regimen, but the Division approved
this change in the DOSAGE AND ADMINISTRATION section of the prescribing
information based upon the current clinical practice and guidelines in order to
clarify the language in the dosing administration . . . The new information
provided by this study, for the purposes of this label, are limited to the content of
its results, which were applied to sections 6 ADVERSE REACTIONS (including
common adverse event profile), 8.5 Geriatric Use and 14 CLINICAL STUDIES
(including clinical success rates).
(Memo from OAP/DAIP re: Sponsor’s Request for Three Year Extension of Exclusivity (Dec.
12, 2011), Part H of Joint Appendix, at FDA004623 (emphasis added).) This information further
affirms the Court’s conclusion. 1

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It is noteworthy that another court in this jurisdiction recently reached the same conclusions that
this Court does regarding the meaning of the 3-year exclusivity provision:
FDA regulations make clear that 3-year exclusivity is not triggered merely by
labeling changes related to the safety or risks posed by the drug for indications
already approved; such changes, if known, would have been incorporated into the
original labeling at the time of the approval of the original NDA. Nor is a 3-year
period of exclusivity triggered by the simple submission of new clinical
investigations or on the applicant’s “say-so.”
AstraZeneca Pharms. LP v. FDA, 872 F. Supp. 2d 60, 66 (D.D.C. 2012).
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III.

VIROPHARMA’S BIOEQUIVALENCE CLAIM
As with its statutory exclusivity claim, ViroPharma fails to present any new arguments or

facts to support its bioequivalence claim. It has merely added two additional examples to
support its previously articulated argument, neither of which compels a different result.
First, ViroPharma asserts that the FDA has removed some of the grounds for waiver that
were listed in § 320.22, and “in doing so reiterated its view that the grounds enumerated there
were exclusive, and do not permit the FDA to excuse in vivo testing in favor of in vitro absent an
applicable ground for waiver.” (Pl. Mot. at 26.) ViroPharma claims that “in notice-andcomment rulemaking to implement Hatch-Waxman, FDA expressly relinquished [the]
discretion” to permit waiver of in vivo testing when the generic drug “‘contains the same active
drug ingredient . . . and is in the same strength and dosage form . . . and both drug products meet
an appropriate in vitro test that has been approved by the [FDA].’” (Pl. Mot. at 26-27 (quoting
54 Fed. Reg. 1624, 1649 (Jan. 7, 1977)) (plaintiff’s emphasis).) However, the FDA convincingly
contests this characterization of its actions, explaining that it sought to remove the blanket
waiver because there was “’no evidence to show that in vitro data alone are regularly sufficient
to assure bioequivalence.’” (Def. Mot. at 38 (quoting 54 Fed. Reg. 28,872, 28,912, (July 10,
1989)) (defendants’ emphasis).) The FDA maintains that its “elimination of a blanket waiver did
not ‘expressly relinquish’ the agency’s statutory discretion to determine for itself the appropriate
bioequivalence method on a case-by-case basis. (Id. (quoting Pl. Mot. at 27) (defendants’
emphasis).)
ViroPharma also suggests that the FDA recognized §320.22 as the sole authority for
waiver of the in vivo requirement when it removed another ground for waiver formerly found at
§ 320.22(b)(3). The FDA “explained that an automatic waiver for all drugs covered by that
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provision was unwarranted – but that removing the automatic waiver did not mean that a waiver
could never be granted[,]” but rather, it would be granted on a case-by-case basis “‘provided the
product meets the [waiver] criteria in 320.22.’” (Pl. Mot. at 27 (quoting 57 Fed. Reg. 17,950,
17,975 (Apr. 28, 1992)) (plaintiff’s emphasis).) Again, ViroPharma reads this history too
expansively, for the agency was speaking only about “applicants’ ability to request waivers
under section 320.22, but [did] not ‘expressly relinquish’ FDA’s statutory discretion to make
independent determinations of the appropriate bioequivalence method, pursuant to subsection
320.24(a).” (Def. Mot. at 38 (defendants’ emphasis).)
Finally, ViroPharma asserts that the FDA again affirmed that the §320.22 criteria must be
met in order to permit in vitro bioequivalence when it corrected a typographical error. The FDA
explained at that time: “Section 320.21(f) inaccurately includes a reference to criteria set forth in
§ 320.24 as containing information under which FDA could waive the requirement for
submission of evidence demonstrating in vivo bioavailability or bioequivalence.” 63 Fed. Reg.
64,222, 64,223 (Nov. 19, 1998). Again, however, ViroPharma makes too much of this fact; the
FDA did not claim to “waive” an in vivo bioequivalence requirement pursuant to 320.24(a) in
this instance. Rather, the FDA was “exercising its authority under subsection 320.24(a) to
determine that in vitro dissolution studies are the ‘most accurate, sensitive, and reproducible
approach’ to determine vancomycin bioequivalence.” (Def. Mot. at 39.) For the reasons set
forth in its Memorandum Opinion, the Court is satisfied that the FDA has not abused its
authority in reaching this determination.
Given the absence of changed facts or new legal arguments or authority, the Court’s
judgment remains the same: the FDA acted well within its discretion in denying three-year
exclusivity to ViroPharma and in approving the ANDAs of intervenor-defendants.

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CONCLUSION
For the foregoing reasons, the Court denies plaintiff ViroPharma’s Motion for Summary
Judgment and grants defendant FDA’s Cross-Motion for Summary Judgment as well as
intervenor-defendants’ Cross-Motion for Summary Judgment. A separate Order accompanies
this Memorandum Opinion.
/s/___________
ELLEN SEGAL HUVELLE
United States District Judge

DATE: January 9, 2013

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