Source: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-caDC-04-05296/USCOURTS-caDC-04-05296-0/pdf.json

Nature of Suit Code: 890
Nature of Suit: Other Statutory Actions
Cause of Action: 

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United States Court of Appeals

FOR THE DISTRICT OF COLUMBIA CIRCUIT

Argued November 8, 2004 Decided November 30, 2004

No. 04-5296

MYLAN LABORATORIES, INC., ET AL.,

APPELLANTS

v.

TOMMY G. THOMPSON, SECRETARY,

UNITED STATES DEPARTMENT OF HEALTH AND

HUMAN SERVICES, ET AL.,

APPELLEES

Appeal from the United States District Court

for the District of Columbia

(No. 04cv01049)

E. Anthony Figg argued the cause for the appellants.

Thomas C. Goldstein was on brief.

Paul F. Brinkman, Amy S. Manning and Thomas J.

Parker were on brief for amicus curiae Generic Pharmaceutical Association in support of appellants.

 Bills of costs must be filed within 14 days after entry of judgment.

The court looks with disfavor upon motions to file bills of costs out

of time.

USCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 1 of 20
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Howard S. Scher, Attorney, United States Department of

Justice, argued the cause for the appellees. Peter D. Keisler,

Assistant Attorney General, Kenneth L. Wainstein, United

States Attorney, Douglas N. Letter, Counsel, United States

Department of Justice, and Alex M. Azar, II, General Counsel, Daniel E. Troy, Chief Counsel, and Eric M. Blumberg,

Deputy Chief Counsel, United States Department of Health

& Human Services, were on brief for federal appellees.

Andrew E. Clark and Karen E. Schifter, Attorneys, United

States Department of Justice, entered appearances.

Anthony Herman, Peter O. Safir, Carolyn F. Corwin and

Kelly M. Jaske were on brief for appellees Alza Corporation

and Janssen Pharmaceutica, Inc.

Bruce N. Kuhlik, David E. Korn and Donald O. Beers

were on brief for amicus curiae Pharmaceutical Research

and Manufacturers of America in support of the appellees.

Gary W. Brown was on brief for amicus curiae Candlelighters Childhood Cancer Foundation National Office in support of the appellees.

Before: EDWARDS and HENDERSON, Circuit Judges, and

WILLIAMS, Senior Circuit Judge.

Opinion for the court filed by Circuit Judge HENDERSON.

KAREN LECRAFT HENDERSON, Circuit Judge: Appellants

Mylan Laboratories, Inc. Mylan Technologies, Inc. and Mylan

Pharmaceuticals, Inc (Mylan) appeal the district court’s summary judgment upholding the decision of appellee Food and

Drug Administration (FDA). The FDA decision granted

appellees ALZA Corp. and Janssen Pharmaceutica, Inc, both

subsidiaries of Johnson and Johnson, (collectively, ALZA) a

six-month period of pediatric marketing exclusivity, pursuant

to 21 U.S.C. § 355a, following expiration of the final patent

for ALZA’s brand name transdermal fentanyl system, the

Duragesic patch, which releases fentanyl, a narcotic analgesic,

through the skin to treat chronic pain. Mylan contends the

FDA’s final approval of Mylan’s Abbreviated New Drug

Applications (ANDA) to market a generic version of the

Duragesic patch, granted before the FDA issued the decision

USCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 2 of 20
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challenged here, entitled Mylan to market its generic product

immediately upon expiration of the patent pursuant to 21

U.S.C. § 355(j), without regard to pediatric exclusivity. For

the reasons set out below, we affirm the district court’s

judgment upholding the FDA’s decision.

I.

This appeal requires that the court consider three separate

statutory provisions: (1) 21 U.S.C. § 355(j), a provision of the

1984 Hatch–Waxman Amendments to the Federal Food,

Drug, and Cosmetic Act (FDCA), which authorizes a drug

manufacturer to submit an ANDA to the FDA to obtain

approval of a generic version of a previously approved drug;

(2) 21 U.S.C. § 355a, a 1997 amendment to the FDCA, which

authorizes an extra six-month ‘‘pediatric exclusivity’’ period

following expiration of a drug patent for a patent holder that

has satisfactorily conducted pediatric testing of its drug upon

the FDA’s request; and (3) 35 U.S.C. § 271(e)(4), a patent

statute, also enacted in the Hatch–Waxman Amendments,

which sets out the exclusive remedies available in a patent

infringement action. We begin with a summary of these

three provisions.

A. Applicable Statutory Provisions

The ANDA provision, 21 U.S.C. § 355(j), creates an approval short-cut for applicants seeking to market generic

versions of approved drugs. Under this provision the generic

applicant need not conduct its own clinical trials if the ANDA

certifies that the generic version is bioequivalent to an approved drug. In addition, the ANDA must include one of

four statutory ‘‘certifications’’ regarding the approved drug’s

patent status:

(I) that such patent information has not been filed,

(II) that such patent has expired,

(III) TTT the date on which such patent will expire, or

USCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 3 of 20
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(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; TTTT

21 U.S.C. § 355(j)(2)(A)(vii)(I)-(IV) (paragraphs I-IV). If the

ANDA contains a paragraph IV certification, the applicant

must, within 20 days of the ANDA filing, send a notice to the

patent holder stating it has submitted an ANDA with the

paragraph IV certification and setting out the factual and

legal bases for believing the patent is invalid or will not be

infringed. 21 U.S.C. § 355(j)(2)(B).

The ANDA provision also establishes the effective date for

approval of the ANDA, depending on the particular certification made.

If the applicant makes a certification under paragraph I or

II, ‘‘the approval may be made effective immediately.’’ 21

U.S.C. § 355(j)(5)(B)(i).

If the certification is under paragraph III, ‘‘the approval

may be made effective on the date certified under [paragraph

III].’’ 21 U.S.C. § 355(j)(5)(B)(ii).

If the certification is under paragraph IV, ‘‘the approval

shall be made effective immediately’’ unless the patent holder

files an infringement action in the district court within 45

days of receiving the notice, in which event ‘‘the approval

shall be made effective upon the expiration of the thirtymonth period beginning on the date of the receipt of the

notice,’’ unless the district court rules on the infringement

claim within the 30-month period. See 21 U.S.C.

§ 355(j)(5)(B)(iii). If the district court issues a ruling during

the 30-month stay period, the ANDA approval date is determined by the decision of the district court, or the appellate

court if appealed.1

1 If the district court decides within the stay period that the

patent is invalid or not infringed, ‘‘the approval shall be made

effective on’’ the date of entry of judgment or of a settlement order

or consent decree. 21 U.S.C. § 355(j)(5)(B)(iii)(I). If the district

court decides the patent is infringed and the judgment is not

appealed or is affirmed, ‘‘the approval shall be made effective on the

date specified by the district court in a court order under section

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The pediatric exclusivity provision, 21 U.S.C. § 355a, provides an incentive for a drug patent holder to conduct pediatric studies of a drug which the FDA believes may have

beneficial pediatric use. Under the statute, the FDA must

first request that the drug patent holder conduct pediatric

studies; if the requested studies are satisfactorily completed

and submitted within the FDA-prescribed time frame, the

patent holder is eligible to receive a six-month period of

market exclusivity for the drug beyond the patent expiration

date. 21 U.S.C. § 355a(c). The pediatric exclusivity provision expressly addresses the effect of a grant of pediatric

exclusivity, depending on the particular certification included

in the ANDA:

(2)(A) if the drug is the subject of–

(i) a listed patent for which a certification has been

submitted under [paragraph II] and for which pediatric studies were submitted prior to the expiration of

the patent (including any patent extensions); or

(ii) a listed patent for which a certification has been

submitted under [paragraph III],

the period during which an application may not be approved under TTT section 355(j)(5)(B) of this title shall be

extended by a period of six months after the date the

patent expires (including any patent extensions); or

(B) if the drug is the subject of a listed patent for

which a certification has been submitted under [paragraph IV], and in the patent infringement litigation

resulting from the certification the court determines that

the patent is valid and would be infringed, the period

during which an application may not be approved under

271(e)(4)(A).’’ Id. § 355(j)(5)(B)(iii)(II)(bb). In turn, if the infringement judgment is appealed, ‘‘the approval shall be made effective

on’’ either ‘‘the date on which the court of appeals decides that the

patent is invalid or not infringed’’ or ‘‘the date of a settlement order

or consent decree signed and entered by the court of appeals

stating that the patent that is the subject of the certification is

invalid or not infringed.’’ Id. § 355(j)(5)(B)(iii)(II)(aa).

USCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 5 of 20
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TTT section 355(j)(5)(B) of this title shall be extended by a

period of six months after the date the patent expires

(including any patent extensions).

21 U.S.C. § 355a(c)(2)(A)-(B).2

Finally, 35 U.S.C. § 271, a patent statute provision, authorizes the following remedies in a patent infringement action:

(4) For an act of infringement described in paragraph

(2)—

(A) the court shall order the effective date of any

approval of the drug or veterinary biological product

involved in the infringement to be a date which is not

earlier than the date of the expiration of the patent

which has been infringed,

(B) injunctive relief may be granted against an infringer to prevent the commercial manufacture, use,

offer to sell, or sale within the United States or

importation into the United States of an approved drug

or veterinary biological product, and

(C) damages or other monetary relief may be

awarded against an infringer only if there has been

commercial manufacture, use, offer to sell, or sale

within the United States or importation into the United States of an approved drug or veterinary biological

product.

The remedies prescribed by subparagraphs (A), (B), and

(C) are the only remedies which may be granted by a

court for an act of infringement described in paragraph

2 If the district court in the patent infringement litigation determines the patent is invalid or will not be infringed, ANDA approval

is effective upon the date of the court order so stating under 21

U.S.C. § 355(j)(5)(B)(iii) and the patent holder is entitled to no

exclusivity thereafter. See, e.g., Mova Pharm. Corp. v. Shalala, 140

F.3d 1060, 1066 (D.C. Cir. 1998).

USCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 6 of 20
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(2), except that a court may award attorney fees under

section 285.

35 U.S.C. § 271(e)(4).

B. This Proceeding

Appellee ALZA owned U.S. Patent No. 4,588,580 (’580

patent) for Duragesic. By its terms the ’580 patent expired

on July 23, 2004.

In July 1999 the FDA wrote ALZA requesting that it

perform pediatric studies of Duragesic pursuant to 21 U.S.C.

§ 355a(c). ALZA submitted the requested studies in November 2002. On January 29, 2003 the FDA granted ALZA a

six-month pediatric exclusivity period.

Meanwhile, in October 2001 Mylan filed with the FDA an

ANDA to market its generic fentanyl transdermal system

pursuant to 21 U.S.C. § 355(j) with a paragraph IV certification that ALZA’s ’580 patent was invalid or would not be

infringed by Mylan’s martketing of its generic product. As

required under 21 U.S.C. § 355(j)(2)(B), on December 6, 2001

Mylan sent ALZA notice of its ANDA application and certification which ALZA received on December 10, 2001. On

January 25, 2002, the forty-sixth day after notice was received, ALZA filed a patent infringement action against Mylan in the United States District Court for the District of

Vermont. Because the action was not brought within the

statutory 45-day window following notice receipt, there was

no automatic 30-month stay and, under 21 U.S.C.

§ 355(j)(5)(B)(iii), Mylan’s ANDA was to ‘‘be made effective

immediately.’’ Accordingly, on November 21, 2003, the FDA

granted final approval of Mylan’s ANDA.

On March 24, 2004 the Vermont District Court issued a

decision holding that ‘‘[t]he ’580 patent is not invalid’’ and

‘‘Mylan’s ANDA filing for a generic version of Duragesic b

infringe[s] TTT the ’580 patent.’’ ALZA v. Mylan, 310 F.

Supp. 2d 610, 637 (D. Vt. 2004). The court therefore enjoined

Mylan from ‘‘making, using, offering to sell, selling within the

United States or importing into the United States’’ its generic

USCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 7 of 20
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fentanyl transdermal system. 310 F. Supp. 2d at 637. Regarding Mylan’s ANDA approval, the court stated simply that

‘‘the effective date of any approval of Mylan’s ANDA product

shall be no earlier than the date of expiration of the ’580

patent family.’’ Id. Mylan appealed the decision to the

Federal Circuit where it remains pending.

In the meantime, both Mylan and ALZA sought a determination from the FDA on whether Mylan could lawfully market its generic fentanyl transdermal system when the ’580

patent expired or whether Mylan was required to wait until

the six-month pediatric exclusivity period expired. In two

letters dated June 22, 2004, the FDA issued its administrative

decision.

In the first letter (Letter 1), addressed to counsel for both

parties, the FDA concluded that ‘‘ALZA’s pediatric exclusivity for fentanyl will attach, and thus delay effective approval of

Mylan’s ANDA,’’ so that ‘‘[u]nless Mylan were to win its

patent case on appeal, Mylan’s ANDA would be eligible for

final effective approval no earlier than six months after

the ’580 patent expires on July 23, 2004.’’ Letter 1 at 11.

The FDA rested its decision on two key determinations.

First, the FDA concluded that the Vermont district court’s

order that ‘‘the effective date of any approval of Mylan’s

ANDA product shall be no earlier than the date of expiration

of the ’580 patent family,’’ 310 F. Supp. 2d at 637, transformed Mylan’s ANDA approval into ‘‘an approval with a

delayed effective date,’’ which ‘‘is a tentative approval that

cannot be made effective until FDA issues a letter granting

final effective approval.’’ Letter 1 at 11 (citing 21 C.F.R.

§ 314.107(b)(3)(v);3

 Barr Labs. v. Thompson, 238 F. Supp. 2d

236, 245-50 (D.D.C. 2002)).

3 This regulation provides:

In order for an approval to be made effective under paragraph

(b)(3) of this section, the applicant must receive an approval

letter from the agency indicating that the application has

received final approval. Tentative approval of an application

USCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 8 of 20
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Second, the FDA concluded that, when ALZA’s patent

expired, Mylan’s paragraph IV certification would no longer

be accurate and Mylan would be required to amend it or, ‘‘[i]f

Mylan refuses to amend its application to change its certification after the patent expires, FDA can treat that certification

as automatically amended to contain a paragraph II certification (because there is no other proper certification upon

expiry).’’ Letter 1 at 12 (citing Ranbaxy Labs. v. FDA, 307

F. Supp. 2d 15, 19, 21 (D.D.C. 2004), aff’d, 96 Fed. App. 1

(D.C. Cir 2004)). Then, once Mylan’s certification converted

to paragraph II, ‘‘pediatric exclusivity attaches under

355a(c)(2)(A)(i),’’ Letter 1 at 12 (citing Ranbaxy, 307 F. Supp.

2d at 20, 21), so that ‘‘ ‘the period during which an [ANDA]

may not be approved TTT shall be extended by a period of six

months after the date the patent expires,’ ’’id. (quoting 21

U.S.C. § 355a(c)(2)(A)(i)).

In the second letter (Letter 2), addressed to Mylan only,

the FDA informed Mylan that, ‘‘in light of [the Vermont

district court’s] decision, the Agency hereby rescinds the final

approval of ANDA 76–258 issued on November 21, 2003, and

regards ANDA 76–258 as tentatively approved.’’ Letter 2 at

1. The letter again noted that, after the Vermont district

court’s order, Mylan’s ANDA approval had ‘‘a delayed effective date,’’ which, by FDA regulation, constitutes ‘‘tentative,’’

rather than ‘‘final,’’ approval. Id. (citing 21 C.F.R.

§ 314.105(a)).4

 Accordingly, the FDA informed Mylan: ‘‘Final Approval cannot be granted earlier than the date of a

court decision finding the patents invalid, not infringed or

unenforceable, or the expiration date of the patent and any

period of pediatric exclusivity granted to the NDA holder.’’

does not constitute ‘‘approval’’ of an application and cannot,

absent a final approval letter from the agency, result in an

effective approval under paragraph (b)(3) of this section.

4 This regulation provides: ‘‘An approval becomes effective on the

date of the issuance of the approval letter, except with regard to an

approval under section 505(b)(2) of the act with a delayed effective

date. An approval with a delayed effective date is tentative and

does not become final until the effective date.’’

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Id. at 1-2 & n.2 (noting that Mylan’s ANDA was ‘‘subject to

ALZA’s pediatric exclusivity for fentanyl transdermal system’’).

On June 24, 2000 Mylan filed this action in the district

court seeking a determination that the FDA’s ‘‘revocation’’ of

Mylan’s final ANDA approval was unlawful and an injunction

prohibiting the FDA ‘‘from revoking the final approval of

Mylan’s ANDA and from applying [ALZA’s] pediatric exclusivity to Mylan’s ANDA.’’ Mylan v. Thompson, 332 F. Supp.

2d 106, 114 (D.C.C. 2004). In a decision filed August 17, 2004

the district court granted summary judgment in the FDA’s

favor, concluding that the agency ‘‘did not improperly revoke

or reclassify its final approval of Mylan’s ANDA for a generic

version of a fentanyl transdermal system to a tentative approval and did not improperly apply ALZA pediatric exclusivity to Mylan’s ANDA.’’ 332 F. Supp. 2d at 124. Mylan

appealed the district court’s summary judgment.

II.

‘‘The court reviews the district court’s summary judgment

decision de novo and ‘we may affirm only if ‘‘there is no

genuine issue as to any material fact [and] the moving party

is entitled to judgment as a matter of law.’’ ’ ’’ Trans Union

LLC v. Fed. Trade Comm’n, 295 F.3d 42, 48 (D.C. Cir. 2002)

(quoting Gilvin v. Fire, 259 F.3d 749, 756 (D.C. Cir 2001)

(quoting Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 250

(1986) (quoting Fed. R. Civ. P. 56(C)))). We review the

FDA’s decision under the Administrative Procedure Act, 5

U.S.C. § 706(2)(A). Serono Labs. v. Shalala, 158 F.3d 1313,

1327 (D.C. Cir. 1998) (citing Troy Corp. v. Browner, 120 F.3d

277, 283 (D.C. Cir. 1997); Schering Corp v. FDA, 51 F.3d 390,

399 (3d Cir. 1995)). Accordingly, we must uphold the FDA’s

decision unless it is ‘‘arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law.’’ 5 U.S.C.

§ 706(2). We conclude that the FDA’s decision was none of

these.

At issue is the FDA’s application of the statutory provisions

summarized above. ‘‘Ordinarily we review an agency’s interUSCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 10 of 20
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pretation of a statute it is charged with implementing under

the familiar and deferential two-part framework of Chevron

U.S.A. Inc. v. Natural Resources Defense Council, Inc., 467

U.S. 837, 104 S.Ct. 2778, 81 L.Ed.2d 694 (1984).’’ Pharm.

Research & Mfrs. of Am. v. Thompson, 362 F.3d 817, 821

(D.C. Cir. 2004). Mylan contends, however, that only minimal

deference is owed to the FDA’s interpretation of the FDCA

because it was expressed in letters to the parties and ‘‘is not

embodied in any regulation, much less a regulation that was

subject to notice and comment rulemaking.’’ Appellants’ Br.

at 19-20. The FDA’s letter decisions, Mylan maintains, are

‘‘analogous to ‘opinion letters,’ ’’ id. at 20 (quoting Skidmore

v. Swift & Co., 323 U.S. 134, 140 (1944)), and therefore ‘‘do

not warrant Chevron-style deference’’ but are entitled only

‘‘ ‘ ‘‘to respect’’ ’ ’’ and even then ‘‘ ‘only to the extent that

those interpretations have the power ‘‘to persuade,’’ ’ ’’ Christensen v. Harris County, 529 U.S. 576, 587 (2000) (quoting

Skidmore, 323 U.S. at 140; other citations omitted)). We are

not persuaded by Mylan’s argument and conclude, as did the

district court, that the FDA’s decision is entitled to Chevron

deference.5

‘‘ ‘[T]he want of’ notice and comment ‘does not decide the

case’ ’’ against Chevron deference. Barnhart v. Walton, 535

U.S. 212, 222 (2002) (quoting United States v. Mead Corp.,

533 U.S. 218, 230-31 (2001)). ‘‘Indeed, Mead pointed to

instances in which the Court has applied Chevron deference

to agency interpretations that did not emerge out of noticeand-comment rulemaking,’’ Id. (citing United States v. Mead

Corp., 533 U.S. at 230-31 (citing NationsBank of N. C., N.A.

v. Variable Annuity Life Ins. Co., 513 U.S. 251, 256-57

5 Mylan also asserts, correctly, that the court owes no deference to the FDA’s interpretation of 35 U.S.C. § 271(e)(4)(A), a

patent statute provision which the FDA is not charged with administering, see Scheduled Airlines Traffic Offices, Inc. v. Dep’t of

Defense, 87 F.3d 1356, 1361 (D.C. Cir. 1996); or of the decision of

the Vermont district court, see American Bioscience v. Thompson,

269 F.3d 1077, 1085 (D.C. Cir. 2001). Neither the statute nor the

court decision, however, presented any ambiguity for the FDA to

interpret.

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(1995))). ‘‘[W]hether a court should give such deference

depends in significant part upon the interpretive method used

and the nature of the question at issue.’’ Id. (citing Mead,

533 U.S. at 229-31). In Barnhardt the Court concluded that

‘‘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 all indicate that

Chevron provides the appropriate legal lens through which to

view the legality of the Agency interpretation here at issue.’’

Id. We reach the same conclusion here.

There is no denying the complexity of the statutory regime

under which the FDA operates, the FDA’s expertise or the

careful craft of the scheme it devised to reconcile the various

statutory provisions. Further, the FDA’s decision made no

great legal leap but relied in large part on its previous

determination of the same or similar issues and on its own

regulations. See Letter 1 at 11-12 (citing 21 C.F.R.

§ 314.107(b)(3)(v), Barr and Ranbaxy); Letter 2 at 1 (citing

21 C.F.R. § 314.105(a)). We therefore accord Chevron deference to the FDA’s letter decision here, as we have previously

done on at least one other occasion. See Abbott Labs. v.

Young, 920 F.2d 984, 986-89 (D.C. Cir. 1990), cert. denied, 502

U.S. 819 (1991) (reviewing under Chevron letter decision

construing term ‘‘active ingredient’’ in ANDA provision, 21

U.S.C. § 355(j)(4)(D)(i), (v)); id. at 992–96 (Edwards, J.,

dissenting) (applying Chevron); see also Barr Labs. v.

Thompson, 238 F. Supp. 2d 236, 245-50 (D.D.C. 2002) (applying Chevron to FDA letter ruling).6

‘‘Under the Chevron framework, ‘[i]f TTT ‘‘Congress has

directly spoken to the precise question at issue,’’ we must give

effect to Congress’s ‘‘unambiguously expressed intent’’ ’ but

6 Even were the FDA’s decision subject only to Skidmore deference, the result would likely be the same. See Ranbaxy Labs. v.

FDA, 96 Fed. App. 1, 1 (D.C. Cir. 2004) (‘‘Regardless whether the

[FDA’s] decision is reviewed under [Skidmore or Chevron], the

district court properly affirmed the FDA’s determinationTTTT’’).

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‘[i]f ‘‘the statute is silent or ambiguous with respect to the

specific issue,’’ we ask whether the agency’s position rests on

a ‘‘permissible construction of the statute.’’ ’ ’’ Pharm. Research & Mfrs., 362 F.3d at 823–24 (quoting Beverly Health &

Rehab. Servs. v. NLRB, 317 F.3d 316, 321 (D.C. Cir. 2003)

(quoting Chevron, 467 U.S. at 842–43). In applying the

FDCA provisions to the particular facts here, the FDA found

two ambiguities.

First, application of the various statutory provisions results

in conflicting effective dates for Mylan’s ANDA. The patent

infringement remedy statute, 35 U.S.C. § 271(e)(4)(A), directs

that the court deciding the infringement action ‘‘shall order

the effective date of any approval of the drug or veterinary

biological product involved in the infringement to be a date

which is not earlier than the date of the expiration of the

patent which has been infringed,’’ which is precisely what the

Vermont district court did here, directing that ‘‘the effective

date of any approval of Mylan’s ANDA product shall be no

earlier than the date of expiration of the ’580 patent family,’’

310 F. Supp. 2d at 637; yet under 21 U.S.C. § 355(j)(5)(B)(iii),

approval of the paragraph IV ANDA was to ‘‘be made

effective immediately’’ after the 45-day window closed without

an infringement action filed by the patent holder, so that the

FDA was required to (and did) grant final approval of Mylan’s ANDA, immediately effective, notwithstanding the pending infringement action. As a result, at the time of the FDA

letter decision, Mylan’s ANDA was subject to two conflicting

approval effective dates: the date of the FDA’s approval

decision (November 21, 2003) and, pursuant to the Vermont

district court’s order, a date ‘‘no earlier than the date of

expiration of the ’580 patent family’’ (i.e., July 23, 2004).

Second, after the Vermont district court’s finding of patent

validity, Mylan’s paragraph IV ANDA certification was at

variance with the legal reality. Because the ’580 patent was

then valid and infringed as a matter of law, ANDA’s certification that the ’580 patent ‘‘is invalid or will not be infringed by

the manufacture, use, or sale of the new drug for which the

application is submitted’’ was no longer accurate. Further,

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section 355a(c)(2), which governs the consequences for pediatric exclusivity under each of the alternative patent certifications, provided no mechanism to resolve this discrepancy

because, at least as construed in the administrative proceeding, this section applies to a paragraph IV certification only if

an infringement action has been filed within the 45-day

window so as to trigger the 30–month stay period.7

 Because

the infringement action here was filed outside the 45-day

window, the FDA was left with a statutory gap to fill.

In deciding the exclusivity issue submitted by Mylan and

ALZA, the FDA was called upon to construe the statutes so

as to resolve these two conflicts. We conclude the FDA did

so in a way that reflects a permissible construction of the

applicable FDCA provisions and therefore satisfies Chevron.

See Western Coal Traffic League v. Surface Transp. Bd., 216

F.3d 1168, 1173 (D.C. Cir. 2000) (reviewing under Chevron

agency resolution of ‘‘unanticipated conflict’’ arising from

application of statute).

A. Conversion of Approval from ‘‘Final’’ to ‘‘Tentative’’

First, the FDA concluded that, as a consequence of the

Vermont district court’s determination under 35 U.S.C.

§ 271(e)(4)(A) that ‘‘the effective date of any approval of

Mylan’s ANDA product shall be no earlier than the date of

expiration of the ’580 patent family,’’ the FDA’s approval of

Mylan’s ANDA was no longer ‘‘immediately effective’’—its

effective date had changed, as the Congress had contemplated it would under such circumstances when it enacted 35

U.S.C. § 271. See H.R. Rep. No. 98-857, pt. 1, at 46 (1984)

(‘‘In the case where an ANDA had been approved, the order

would mandate a change in the effective date.’’). The FDA

7 On appeal the appellees argue alternatively that section

355a(c)(2)(B) can be read to cover the situation when the action is

filed after the 45-day window as well as before (obviating the need

for certification conversion). This may well be a permissible construction of the provision but it is not the reading the FDA applied

during the administrative proceeding nor the one before us on

review of the FDA’s decision.

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next determined, logically enough, that the effective date was

then ‘‘delayed’’ and therefore ‘‘tentative,’’ rather than ‘‘immediate’’ and ‘‘final,’’ under the FDA’s own regulation which

provides that ‘‘[a]n approval with a delayed effective date is

tentative and does not become final until the effective date.’’

21 C.F.R. § 314.105(a); see Barr Labs. v. Thompson, 238 F.

Supp. 2d 236, 245-50 (D.D.C. 2002) (upholding FDA determination under 21 C.F.R. § 314.105(a) that ANDA approval

before patent expiration was tentative, not final).

Mylan contends the FDA lacked authority to revoke Mylan’s final ANDA approval granted on November 21, 2003

because its authority to revoke a final approval is limited to

those specific circumstances set out in 21 U.S.C. § 355(e),

none of which exists here. Mylan’s characterization of section 355(e) is off the mark. As the FDA indicates in its

decision, Letter 1 at 12 n.10, section 355(e) simply sets out

specific, not necessarily exclusive, circumstances under which

the FDA must withdraw any ANDA approval (whether final

or otherwise) after notice and hearing. But the provision

does not prohibit the FDA from withdrawing approval under

other circumstances—or, more precisely, does not prohibit

the FDA from changing a final into a tentative approval

under circumstances different from those named in section

355(e).8

 Moreover, the patent remedy statute directs that

upon a finding of infringement the district court establish a

new effective date for approval which is ‘‘not earlier than the

date of the expiration of the patent which has been infringed.’’

35 U.S.C. § 271(e)(4)(A), and the FDA was bound under the

district court’s order to treat the status of Mylan’s ANDA

under the FDCA ‘‘the same as that of other ANDAs blocked

from final approval by patent or exclusivity rights.’’ Letter 1

at 12 n.10.

8 We are skeptical whether the parties properly characterize the

FDA’s action as ‘‘withdrawal’’ or ‘‘revocation’’ of approval. It seems

to us that Mylan’s ANDA approval was never in fact ‘‘withdrawn’’

or ‘‘revoked’’ but remained continuously in effect based on the

FDA’s review of the ANDA described in the November 21, 2003

final approval letter. The approval merely underwent a change of

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Mylan also claims the approval conversion is ‘‘contrary to

past Agency practice.’’ Appellants’ Br. 43 (citing Mead Johnson Pharm. Group v. Bowen, 838 F.2d 1332, 1334 (D.C. Cir.

1988), and Unimed, Inc. v. Quigg, 888 F.2d 826, 827 (Fed.

Cir. 1989)). Each cited case, however, involved not an ANDA

but a New Drug Application, a different animal entirely

because the latter is generally not subject to a delayed

effective date, and each application was subject to an approval

letter authorizing immediate marketing without any delayed

effective date. See Mead Johnson, 838 F.2d at 1336 (noting

applicant could have marketed its product on day of approval

by filing required supplemental labeling); Unimed, 888 F.2d

at 828 (FDA letter noting product could not be marketed

until it was ‘‘rescheduled’’ by DEA simply ‘‘reminded Unimed

that DEA rescheduling was necessary before the drug could

be marketed’’ and ‘‘was not a condition on FDA approval’’)

(emphasis original).9

B. Conversion of Paragraph IV to

Paragraph II Certification

The FDA next addressed the problem of Mylan’s inaccurate ANDA certification and resolved it relying on Ranbaxy

Labs. v. FDA, 307 F. Supp. 2d 15 (D.D.C. 2004), aff’d, 96 Fed.

App. 1 (D.C. Cir 2004). The FDA concluded that under

Ranbaxy when the ’580 patent expired, Mylan’s paragraph IV

certification would convert to a paragraph II certification and

ALZA would be entitled to pediatric exclusivity for six

months following the expiration. The FDA reasoned that

status or classification from final to tentative after the Vermont

district court delayed its effective date.

9 Nor do we see any force in Mylan’s citation to the FDA’s 1994

rulemaking, in which the FDA declined to extend by rule the

statutory 45-day window. Appellants’ Br. at 42 (quoting 59 Fed.

Reg. at 50,353). The FDA simply explained there that if the

window were to be extended (which it was not), the FDA would

retain authority during the extension to grant final effective ANDA

approval, notwithstanding the patent holder might subsequently file

a successful infringement action.

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once the certification became inaccurate, Mylan was under a

duty to amend its ANDA to change the certification to

paragraph II, see 21 C.F.R. § 314.94(a)(12)(viii)(C)(i) (providing ‘‘an applicant shall amend a submitted certification if, at

any time before the effective date of the approval of the

application, the applicant learns that the submitted certification is no longer accurate’’); and if Mylan failed to do so, the

FDA could ‘‘treat that certification as automatically amended

to contain a paragraph II certification.’’ Letter 1 at 12.

Once the certification changed to paragraph II—whether de

facto or de jure—pediatric exclusivity attached under 21

U.S.C. § 355a(c)(2)(A)(i) (‘‘[I]f the drug is the subject of– TTT

a listed patent for which a certification has been submitted

under [paragraph II] and for which pediatric studies were

submitted prior to the expiration of the patent; TTT the

period during which an application may not be approved

under TTT section 355(j)(5)(B) of this title shall be extended

by a period of six months after the date the patent expires.’’).

We find the FDA’s application of the statutory provisions

both reasonable and supported by Ranbaxy.

In Ranbaxy the FDA also converted an ANDA classification from a paragraph IV to a paragraph II certification

under similar circumstances. The patent holder in Ranbaxy

filed an infringement action within forty-five days after receiving the required paragraph IV certification notice. Upon

learning the district court would be unable to decide the case

before the patent expiration date, the parties signed a stipulation to dismiss the action as of the expiration date. The day

before expiration, the FDA informed the ANDA applicant

that its ANDA would be subject to a six-month pediatric

exclusivity period for the patented drug. There, as here, 21

U.S.C. § 355a(c)(2)(B) did not apply (there, because there was

no finding of a valid patent or infringement) and the FDA

concluded that upon the patent expiry the paragraph IV

certification converted to a paragraph II certification and

pediatric exclusivity attached under 21 U.S.C.

§ 355a(c)(2)(A)(i). The district court agreed with the FDA’s

statutory construction and on appeal we concluded:

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[T]he district court properly affirmed the FDA’s determination that, under the Federal Food, Drug, and Cosmetic

Act, 21 U.S.C. § 301, et seq., final approval of Ranbaxy’s

Abbreviated New Drug Applications (‘‘ANDAs’’) did not

automatically occur upon the dismissal of the underlying

patent litigation, the expiration of the patent, and the

termination of the thirty-month statutory stay. The

district court also properly affirmed the FDA’s conclusion that, upon the expiration of Pfizer’s patent on January 29, 2004, Ranbaxy’s ‘‘Paragraph IV’’ certifications

became invalid, and the applicable pediatric exclusivity

provision became 21 U.S.C. § 355a(c)(2)(A), the provision

pertaining to ‘‘Paragraph II’’ certifications. Id. Under

that provision, approval of Ranbaxy’s ANDAs is delayed

six monthsTTTT See 21 U.S.C. § 355a(c)(2)(A).

96 Fed. App. at 1. For the same reasons, the district court

here acted properly in upholding the FDA’s certification

conversion.

Mylan contends that one of the FDA’s own regulations

weighs against this rationale, namely, 21 C.F.R.

§ 314.94(a)(12)(viii)(A), which requires that an ANDA applicant amend its application to recertify under paragraph III

(‘‘that the patent will expire on a particular date’’) if a finding

of validity/infringement is made in a lawsuit that has been

filed within the statutory 45-day window. Mylan asserts the

‘‘necessary implication’’ of this language is that ‘‘if the applicant is not sued within the forty-five-day-period, 21 U.S.C.

§ 355(j)(5)(B)(iii) requires that approval of an ANDA shall be

‘effective immediately’ and certifications are no longer relevant.’’ Appellants’ Br. at 42. Mylan reads too much into the

regulation. That the FDA has expressly required recertification when an action is filed within the 45-day window does not

‘‘necessarily’’ mean an applicant need not amend its application to change the patent certification to reflect changed

circumstances if the action is not filed within the window. To

the extent that the cited regulation is relevant here, it supports the FDA’s rationale in requiring a generic drug appliUSCA Case #04-5296 Document #862632 Filed: 11/30/2004 Page 18 of 20
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cant to amend its ANDA to include an accurate certification.10

Mylan also contends the FDA’s construction ‘‘would read

[section 355a(c)(2)(B)] entirely out of the statute’’ because, if

it ‘‘does not govern the availability of pediatric exclusivity in

cases like this one involving Paragraph IV certifications in

which infringement is found, the statute serves no purpose at

all.’’ Appellants’ Br. at 22-23. Not so. Under the FDA’s

interpretation, section 355a(c)(2)(B) applies when—and only

when—all three of its express conditions are met: ‘‘a certification has been submitted under [paragraph IV],’’ there is

‘‘patent infringement litigation resulting from the certification’’ and in the litigation ‘‘the court determines that the

patent is valid and would be infringed.’’ It is only because

one of these requirements was missing in Ranbaxy (a valid

patent finding) and in this case (an infringement action filed

within the 45-day window) that the FDA, prevented from

applying its reading of section 355a(c)(2)(B), was required to

fill the statutory gap by deeming the patent certification

changed.

* * *

We affirm the district court’s judgment because the FDA’s

decision reasonably resolves the ambiguity in applying the

relevant statutes to a factual situation not fully foreseen or

provided for by the Congress when it enacted the statutes or

the FDA when it promulgated regulations. The Vermont

district court’s finding of patent validity and consequent

injunction changed the factual and legal landscape and the

agency’s response to the court’s decision is both reasonable

and consistent with the statutory language. The FDA’s

10 The FDA might well have concluded that in this situation too,

as ALZA suggested in the administrative proceeding, see Letter 1

at 11, the paragraph IV certification should have changed to a

paragraph III certification immediately upon the district court’s

finding of validity/infringement, consistent with the directive of 21

C.F.R. § 314.94(a)(12)(viii)(C)(1)(i) that ‘‘an applicant shall amend a

submitted certification if, at any time before the effective date of

the approval of the application, the applicant learns that the submitted certification is no longer accurate.’’

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solution effects the policies of both the generic ANDA provision, by eliminating the need for Mylan to conduct clinical

trials of its generic product, and the pediatric exclusivity

provision, by granting ALZA a six-month exclusivity period in

return for the pediatric studies it performed, the adequacy of

which Mylan does not dispute. At the same time, it maintains the incentive under 21 U.S.C. § 355(j)(5)(B)(iii) for a

patent holder to promptly file an infringement action when its

patent is challenged because, if the patent holder fails to do

so within forty-five days, it will lose the benefit of the 30-

month stay period and possibly, for a time, market exclusivity

it should rightfully enjoy.11

So ordered.

11 In a case such as this, for example, if the district court found

the patent invalid, without the 30–month stay the ANDA applicant

would obtain immediate approval under the court’s decision to

market its generic product notwithstanding the patent holder might

subsequently successfully appeal the district court’s decision.

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