Source: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-caDC-98-05151/USCOURTS-caDC-98-05151-0/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 February 1, 1999 Decided July 16, 1999

No. 98-5151

Pfizer Inc.,

Appellant

v.

Donna E. Shalala, Secretary,

U.S. Department of Health and Human Services, et al.,

Appellees

Appeal from the United States District Court

for the District of Columbia

(No. 97cv01554)

Bert W. Rein argued the cause for appellant. With him on

the briefs were Andrew S. Krulwich, Bruce G. Joseph and

Michael L. Sturm.

Drake Cutini, Attorney, U.S. Department of Justice, argued the cause for appellees. With him on the brief was

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Frank W. Hunger, Assistant Attorney General. Gerald C.

Kell, Attorney, entered an appearance.

E. Anthony Figg argued the cause for appellee Mylan

Pharmaceuticals, Inc. With him on the brief was Steven

Lieberman.

David G. Adams was on the brief for appellee Penwest

Pharmaceuticals Group. David M. Malone and Lawrence B.

Bernard entered appearances.

David F. Weeda and David L. Durkin were on the brief for

amicus curiae National Association of Pharmaceutical Manufacturers.

Before: Edwards, Chief Judge, Ginsburg, and Tatel,

Circuit Judges.

Opinion for the Court filed by Circuit Judge Ginsburg.

Ginsburg, Circuit Judge: Pfizer, Inc. manufactures and

sells the pioneer drug Procardia XLR, which contains the

active ingredient nifedipine, a calcium-blocker used to treat

angina and hypertension. Procardia XLR uses a patented

"osmotic pump" to control the extended release of nifedipine.

Mylan Pharmaceuticals, Inc. filed an abbreviated new drug

application (ANDA) with the Food and Drug Administration

seeking approval of its own extended release nifedipine product as a generic "pharmaceutical equivalent" to Procardia

XLR; Mylan's product, however, uses an extended release

mechanism different from Pfizer's osmotic pump. Despite

the different mechanisms the FDA accepted Mylan's ANDA

for processing but has not yet decided whether to approve it.

Pfizer claims, as it did in a so-called "citizen petition" filed

with the FDA before Mylan had sought approval for its drug,

that the osmotic pump is a unique "dosage form." 21 U.S.C.

s 355(j)(2)(A)(iii). It therefore follows, according to Pfizer,

that the FDA must reject Mylan's ANDA. The FDA and

intervenors Mylan and Penwest Pharmaceuticals Group,

which developed the extended release mechanism used in

Mylan's drug, argue that the agency's decision is not ripe for

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judicial review. For the reasons below, we agree with the

agency and dismiss Pfizer's petition for review.

I. Background

A. Statutory and Regulatory Framework

The approval of the FDA is required before any drug may

be marketed in the United States. See 21 U.S.C. s 355(a).

The sponsor of a new drug ordinarily must undertake expensive and time-consuming clinical (that is, human) studies in

order to show that its new drug is safe and effective for its

intended use. See id. s 355(b). Once the FDA approves a

new drug, however, a competitor seeking to market a generic

version may file an ANDA, relying upon the clinical findings

the FDA has already approved with respect to the pioneer

drug. See id. s 355(j).

In order to gain approval of an ANDA, an applicant must

show that its generic drug is "bioequivalent to the listed

[pioneer] drug." Id. s 355(j)(4)(F). Bioequivalence refers

generally to the rate at which, and the extent to which, the

body absorbs the active ingredient(s) in the drug. See id.

s 355(j)(8); 21 C.F.R. s 320.1(e).

To gain approval as a "pharmaceutical equivalent," 21

C.F.R. s 320.1(c), an applicant must additionally "show that

the active ingredient ..., the route of administration, the

dosage form, and the strength of the new drug are the same

as those of the listed [pioneer] drug." 21 U.S.C.

s 355(j)(2)(A)(ii)-(iii); see also id. s 355(j)(4)(C)-(D). If the

generic drug differs from the pioneer drug in any of those

four respects, then the manufacturer may still avail itself of

the ANDA process by filing a "suitability petition," see id.

s 355(j)(2)(C), upon the basis of which its product could be

approved as a "pharmaceutical alternative" to the pioneer

drug. 21 C.F.R. s 320.1(d). The distinction is significant

because many states permit only a pharmaceutical equivalent

to be substituted for the pioneer drug, and Medicaid and

many insurance plans do not reimburse patients for the cost

of a pharmaceutical alternative.

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The FDA first reviews an ANDA (whether submitted for

approval as a pharmaceutical equivalent or as a pharmaceutical alternative) in order to determine whether it may be

"received," i.e., accepted for processing, for which the standard is that "the abbreviated application is sufficiently complete to permit a substantive review." Id. s 314.101(b)(1);

see also id. (d)(3) (FDA may reject ANDA if incomplete "on

its face"). If, upon substantive review, the FDA finds the

generic drug satisfies all of the applicable statutory requirements, then it must approve the ANDA. See 21 U.S.C.

s 355(j)(4).

The FDA publishes a current list of all approved drugs,

known as the "Orange Book." See U.S. Dep't of Health &

Human Serv., Approved Drug Products With Therapeutic

Equivalence Evaluations (17th ed. 1997). In an appendix to

the Orange Book the FDA lists 74 dosage forms. Among

these are aerosols, implants, capsules, and seven types of

tablets, including chewable, dispersible, effervescent, and the

one with which we are concerned, "extended release."

B. Pfizer's Claims

The FDA approved Pfizer's new drug application for Procardia XLR in 1989 and listed it in the 1990 Orange Book as

having the dosage form "tablet, extended release; oral." As

mentioned, the extended release mechanism in Procardia

XLR is a patented osmotic pump. As fluid from the gastrointestinal tract enters the shell of the tablet, it dissolves

the active ingredient, nifedipine, and causes a "push" layer to

swell, thereby gradually expelling the nifedipine into the

gastrointestinal tract through a hole in the shell. Compl.

p 20.

In 1993 Pfizer filed a "citizen petition" with the FDA,

pursuant to 21 C.F.R. s 10.30, asking the agency to recognize

Pfizer's "oral osmotic pump [as] a distinct dosage form."

Pfizer also contended the agency must require a suitability

petition if a generic drug "uses a different mechanism of

release from the reference drug."

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The FDA had not ruled upon Pfizer's petition when, nearly

four years later, Mylan submitted an ANDA for an extended

release nifedipine tablet claiming pharmaceutical equivalence

to Procardia XLR. The FDA accepted Mylan's application

for processing even though its tablet uses a different extended release mechanism than does Procardia XLR.

After failing to persuade the agency to stay or to withdraw

its acceptance of Mylan's ANDA, Pfizer filed this suit in the

district court challenging that acceptance as arbitrary, capricious, and contrary to law. In a second count Pfizer repeated

the claim, first made in its still-pending citizen petition, that

the FDA was obliged to recognize its osmotic pump as a

distinct dosage form. Shortly thereafter the FDA denied

Pfizer's citizen petition.

The district court held that Pfizer's challenge to the FDA's

receipt of Mylan's application was unripe because the agency

had not yet decided whether to approve Mylan's generic drug.

See Pfizer Inc. v. Shalala, 1 F. Supp. 2d 38, 44 (1998). On

the other hand, the court held that the FDA's denial of

Pfizer's citizen petition was "final agency action," and therefore ripe for review. Id. On the merits of that claim, the

district court upheld as rational and consistent with the

statute the FDA's refusal to treat Pfizer's osmotic pump as a

distinct form of dosage. See id. at 44-48.

II. Analysis

The FDA contends that neither its acceptance of Mylan's

ANDA for processing nor its denial of Pfizer's citizen petition

caused Pfizer injury sufficiently imminent to confer jurisdiction upon the court. Pfizer responds that it is "imminently

threatened with economic injury from unlawful competition."

So are Pfizer's claims ripe for judicial review or not?

Here is what the Supreme Court said last Term by way of

summarizing the ripeness doctrine. In order to determine

whether a controversy is ripe a court must "evaluate both the

fitness of the issues for judicial decision and the hardship to

the parties of withholding court consideration." Texas v.

United States, 523 U.S. 296, 301 (1998). "A claim is not ripe

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for adjudication if it rests upon contingent future events that

may not occur as anticipated, or indeed may not occur at all."

Id. at 300. Thus, the ripeness requirement serves "to prevent the courts, through avoidance of premature adjudication,

from entangling themselves in abstract disagreements over

administrative policies, and also to protect the agencies from

judicial interference until an administrative decision has been

formalized and its effects felt in a concrete way by the

challenging parties." Ohio Forestry Ass'n v. Sierra Club, 523

U.S. 726, 732-33 (1998) (quoting Abbott Labs. v. Gardner, 387

U.S. 136, 148-49 (1967)).

We assess first Pfizer's challenge to the FDA's acceptance

of Mylan's ANDA for processing. Pfizer claims the agency's

action is final and therefore fit for review because once having

decided, based upon the information contained in Mylan's

application, that Mylan's drug uses the same dosage form as

Procardia XLR, the FDA will not "alter its views with

respect to the necessity of Mylan filing a suitability petition."

The decision to accept Mylan's ANDA for processing as a

pharmaceutical equivalent to Procardia XLR is, however,

merely the first step in the agency's approval process. The

critical fact remains that the FDA may never approve Mylan's application--whether because it decides in the end that

the dosage form of Mylan's drug is different from that of

Procardia XLR or for some entirely different reason, such as

a lack of bioequivalence. Therefore, "depending upon the

agency's future actions ... review now may turn out to have

been unnecessary" and could deprive the agency of the

opportunity to apply its expertise and to correct any mistakes

it may have made. Id. at 736 (holding challenge to agency's

logging plan unripe when no specific area was yet identified

for harvesting and agency might revise or modify plan).

Pfizer contends the FDA's own regulations demonstrate

that it does not consider its acceptance of an ANDA for

processing to be a "tentative" decision because it gives the

first person to file a generic application (here Mylan) a 180-

day marketing priority as against any later-filed generic

application. See 21 C.F.R. s 314.107(c). In other words,

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says Pfizer, the agency's acceptance of Mylan's ANDA "affects the legal rights of all subsequent applicants referencing

Procardia XLR." We find this argument doubly unpersuasive. First, it assumes its own conclusion, for Mylan will get

the 180-day marketing priority only if its application is finally

approved. Second, the legal rights that will be affected are

not Pfizer's but those of its competitors, about which Pfizer is

not in a position to complain.

Nor can Pfizer point to any imminent hardship arising from

the FDA's acceptance of Mylan's ANDA. Before Pfizer could

suffer its claimed "economic injury from unlawful competition," FDA approval for a pharmaceutical equivalent to Procardia XLR would have to be not only sought but granted.

That has not happened. Therefore "no irremediable adverse

consequences flow from requiring a later challenge." Toilet

Goods Ass'n v. Gardner, 387 U.S. 158, 164 (1967). This case

might nonetheless be ripe if the FDA's acceptance of Mylan's

ANDA for processing somehow foreclosed Pfizer's right ever

to get meaningful judicial review, but it does not. If the FDA

eventually approves Mylan's application, Pfizer may then

challenge the reasons underlying its final decision, including

the agency's interpretation of the statutory term "dosage

form."

Pfizer next suggests that the agency's acceptance of Mylan's ANDA for processing compelled it to sue Mylan for

patent infringement and thereby to incur the burden of

litigation expenses. Not so. Pursuant to the Drug Price

Competition and Patent Term Restoration Act of 1984, which

established the ANDA procedure, see Pub. L. No. 98-417, 98

Stat. 1585, the owner of a pioneer drug may, by suing the

sponsor of the ANDA for patent infringement, cause the FDA

to stay its approval of a generic drug for 30 months. See 21

U.S.C. s 355(j)(5)(B)(iii). To get the benefit of the stay, such

a suit must be filed within 45 days after the owners of the

pioneer drug and of any associated patents receive notice

from the sponsor of the ANDA claiming that the pioneer's

patents are either "invalid or will not be infringed" by the

generic drug. Id. s 355(j)(2)(A)(vii)(IV). Nothing in the Act,

however, precludes the owner of a pioneer drug from waiting

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longer than 45 days to sue for patent infringement. Therefore, Pfizer voluntarily incurred the expense of preemptive

patent litigation in order to get a substantial statutory benefit, namely, a stay of the FDA's approval of Mylan's ANDA.

In sum, Pfizer suffers no hardship because it "is not required

to engage in, or to refrain from, any conduct." Texas, 523

U.S. at 301. We therefore hold the FDA's acceptance for

processing of Mylan's ANDA is not ripe for judicial review at

this time.

If the FDA's acceptance of Mylan's ANDA is not ripe, then

it follows a fortiori that the FDA's denial of Pfizer's citizen

petition is not ripe. Pfizer raises precisely the same objection

to both agency actions, namely, that the FDA erred in

interpreting the statutory term "dosage form." But in denying Pfizer's citizen petition, the FDA did not apply that

interpretation to a particular set of facts, as it did in accepting Mylan's ANDA for processing. Rather, it simply refused

to affirm the negative proposition that no other extended

release mechanism could ever be deemed under the statute to

constitute the same dosage form as Pfizer's osmotic pump.

Therefore Pfizer's challenge to the agency's refusal to recognize its osmotic pump as a unique dosage form raises just the

sort of abstract disagreement over an administrative policy at

which the ripeness doctrine is aimed. See Ohio Forestry, 523

U.S. at 736. "Here, as is often true, determination of the

scope of legislation in advance of its immediate adverse effect

in the context of a concrete case involves too remote and

abstract an inquiry for the proper exercise of the judicial

function." Texas, 523 U.S. at 301.

Pfizer defends its ground by pointing to an FDA regulation

that deems the agency's response to a citizen petition a "final

agency action ... reviewable in the courts," 21 C.F.R.

s 10.45(d); but a final agency action nonetheless can be

unripe for judicial review. See Mount Wilson FM Broad. v.

FCC, 884 F.2d 1462, 1465 (D.C. Cir. 1989). Ripeness entails a

functional, not a formal, inquiry. An administrative agency,

which is not subject to Article III of the Constitution of the

United States and related prudential limitations, may issue a

declaratory order in mere anticipation of a controversy or

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simply to resolve an uncertainty. See Metropolitan Council

of NAACP Branches v. FCC, 46 F.3d 1154, 1161 (D.C. Cir.

1995). An Article III court, however, may not adjudicate a

dispute until it has both crystallized as an actual "case or

controversy" and satisfied the prudential requirements of the

ripeness doctrine. See Reno v. Catholic Social Servs., Inc.,

509 U.S. 43, 57 n.18 (1993) (explaining "ripeness doctrine is

drawn both from Article III limitations on judicial power and

from prudential reasons for refusing to exercise jurisdiction").

* * *

After oral argument of this case the FDA tentatively

approved Mylan's ANDA. The agency conditioned its final

approval upon both the expiration of the 30-month period

established in 21 U.S.C. s 355(j)(5)(B)(iii), during which the

agency is prohibited from approving Mylan's new drug, and

assurance from Mylan that there is no new information

affecting whether final approval should be granted. Pfizer

argues that this development ripens its challenge to the

FDA's acceptance of Mylan's application for processing because the agency contemplates no additional substantive analysis of Mylan's application. See Regional Rail Reorganization Act Cases, 419 U.S. 102, 140 (1974) (holding that "since

ripeness is peculiarly a question of timing, it is the situation

now rather than the situation at the time of the District

Court's decision that must govern").

We agree, however, with the FDA's contention that Pfizer's

challenge is still unripe. Although it is now more likely that

the FDA will eventually approve Mylan's drug, the agency's

tentative approval causes Pfizer no hardship at present or in

the near future, nor does it render Pfizer's challenge fit for

review. See Texas, 523 U.S. at 300 (holding case unripe even

assuming greater certainty of adverse action resting upon

future contingent events).

As to hardship, nothing untoward can happen to Pfizer

until at least December 1999, when the 30-month period

triggered by the filing of its patent suit against Mylan expires

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and the FDA (assuming no change of circumstances) may

issue a final approval.* As to fitness, should we dismiss as

unripe Pfizer's present challenge to the FDA's acceptance for

processing of Mylan's ANDA, then Pfizer could not only

renew that claim, which is based solely upon the FDA's

interpretation of the statutory dosage form requirement, it

could also bring in the same action any other claim that may

arise from the agency's final approval--if and when it is

given--such as lack of bioequivalence. Accordingly, judicial

intervention at this time could lead to "piecemeal review

which at the least is inefficient and upon completion of the

agency process might prove to have been unnecessary." FTC

v. Standard Oil Co., 449 U.S. 232, 242 (1980).

III. Conclusion

We hold that Pfizer's challenges to the FDA's acceptance

for processing of Mylan's ANDA and to its denial of Pfizer's

citizen petition are both unripe for review. The judgment of

the district court is therefore

Affirmed in part and reversed in part.

* Neither party claims there is any likelihood that the patent suit

will be dismissed or settled at an earlier date.

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