Source: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-caDC-99-05048/USCOURTS-caDC-99-05048-0/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 September 17, 1999 Decided February 11, 2000

No. 99-5048

Warner-Lambert Company,

Appellant

v.

Donna E. Shalala, Secretary of Health

and Human Services, et al.,

Appellees

Appeal from the United States District Court

for the District of Columbia

(No. 99cv00093)

Bruce N. Kuhlik argued the cause for appellant. With him

on the briefs were Herbert Dym, Michael S. Labson, and

Michael A. Listgarten.

Jeffrey B. Chasnow, Attorney, U.S. Department of Justice,

argued the cause for appellees Donna E. Shalala, et al. With

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him on the brief was David W. Ogden, Acting Assistant

Attorney General.

E. Anthony Figg argued the cause for appellee Mylan

Pharmaceuticals, Inc. With him on the brief was Bart G.

Newland. Steven M. Lieberman entered an appearance.

Before: Williams, Rogers and Garland, Circuit Judges.*

Opinion for the Court filed by Circuit Judge Williams.

Williams, Circuit Judge: When is a pill a capsule rather

than a tablet? Plaintiff Warner-Lambert's entitlement to

relief against the Food and Drug Administration turns on this

point. Warner-Lambert believes that an anti-epilepsy drug

made by Mylan Pharmaceuticals--having the interior form of

a tablet but placed inside a capsule--cannot properly be

viewed as a capsule. The Mylan product therefore has,

according to Warner-Lambert, a different "dosage form"

from that of Warner-Lambert's anti-epilepsy drug "Dilantin."1 If Warner-Lambert is right, then the FDA should not

have found the Mylan product "therapeutically equivalent" to

Dilantin and (without putting Mylan's product through additional hoops) should not have approved Mylan's "abbreviated

new drug application." And, again if Warner-Lambert is

right, it would likely be entitled to the district court injunction that it sought, forcing the FDA to withdraw its finding of

equivalence and to rescind its approval of the Mylan product.

Because Warner-Lambert has not convinced us of any legal

error in the FDA's decision on the capsule-tablet issue, we

affirm the denial of the preliminary injunction.

__________

* Circuit Judge Garland was originally a member of the panel but

did not participate in the opinion in this case.

1. Dilantin is the brand name of a family of anti-epilepsy drugs

manufactured by Warner-Lambert's Parke-Davis division. The

drug at issue here is the largest-selling of the Dilantin line, the 100

mg strength of extended phenytoin sodium capsules marketed as

Dilantin Kapseals. For simplicity, we adopt Warner-Lambert's

terminology and refer to the Dilantin Kapseals product simply as

"Dilantin."

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* * *

The FDA must find a new drug to be safe and effective for

its intended use before any person may introduce it into

interstate commerce. See 21 U.S.C. s 355(a) (1994). The

first, or "pioneer," applicant for a given drug must submit a

new drug application ("NDA"), which includes "full reports of

investigations which have been made to show whether or not

such drug is safe for use and whether such drug is effective in

use." Id. s 355(b). Once the FDA approves the application

for the pioneer drug, it becomes a "listed drug," id.

s 355(j)(7), and generic copies may be approved using the far

simpler, abbreviated new drug application ("ANDA"), id.

s 355(j)(2)(A)(ii)-(iv).

An ANDA will be approved if the applicant demonstrates

that the generic drug is bioequivalent to the listed drug and

has the same active ingredients, route of administration,

strength, and dosage form. See id. s 355(j)(2)(A)(ii)-(iv),

(j)(4); see also 21 CFR s 314.92(a)(1) (1999) (indicating the

categories of drug products for which ANDAs may be filed).

If the drug is different in any of these four respects, a generic

manufacturer may use an abbreviated application only if it

first files a "suitability petition" and the FDA grants it

permission to file an ANDA. 21 U.S.C. s 355(j)(2)(C); 21

CFR s 314.93. The petition must be granted unless the FDA

finds that the difference calls the safety and effectiveness of

the drug into doubt. See 21 U.S.C. s 355(j)(2)(C). But

drugs that require a suitability petition cannot be considered

"therapeutically equivalent"2 to the pioneer drug, and therefore cannot take advantage of state pharmacy laws that deem

such products substitutable. See Serono Labs. v. Shalala,

158 F.3d 1313, 1317 (D.C. Cir. 1998). Substitutability is

competitively important. When a doctor prescribes a drug by

brand name, the pharmacist may (and in some states must)

__________

2. Therapeutic equivalence turns on "pharmaceutical equivalence" which is based in part upon identity of dosage form. Pharmaceutical equivalence is defined in FDA regulations, see 21 CFR

s 320.1(c), and an FDA publication known as the Orange Book,

available on the FDA's web site, see <http://www.fda.gov/cder/ob>.

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dispense a therapeutically equivalent generic alternative unless the doctor requires that the prescription be dispensed as

written. See, e.g., N.Y. Educ. Law s 6816-a (McKinney

1999) (requiring generic drug substitution unless the doctor

indicates otherwise).

Mylan Pharmaceuticals, Inc. filed an ANDA for its 100

milligram phenytoin sodium product, which it said satisfied

the criteria for approval as a generic version of Dilantin. The

FDA issued an approval letter on December 28, 1998, finding

the product therapeutically equivalent to Dilantin. In so

holding, it necessarily found that Mylan's product had the

same dosage form as Dilantin, i.e., was in the form of a

capsule.

Because the ANDA process is not public, the approval

letter was Warner-Lambert's first notice of Mylan's application. But Warner-Lambert rose quickly to the challenge.

Two weeks later it filed a complaint and request for preliminary injunction in the district court. All its claims rested on

the argument that Mylan's product is properly classified as a

tablet rather than a capsule. More specifically, however,

Warner-Lambert argued that the FDA violated the statute

by failing to apply the definitions of the United States Pharmacopoeia ("USP") for particular dosage forms as required

by the Food, Drug and Cosmetic Act (under which, WarnerLambert urges, Mylan's product would be a tablet), and acted

arbitrarily and capriciously by classifying Mylan's product as

a capsule when it has previously classified indistinguishable

products as tablets.

The district court disagreed and denied Warner-Lambert's

preliminary injunction request on January 29, 1999, in a

ruling from the bench. Warner-Lambert filed a timely notice

of appeal.

* * *

It is commonly said that we review a district court's

decision to deny a preliminary injunction under the deferential "clear error" or "abuse of discretion" standards, due to

the "latitude the district court properly enjoys in balancing

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the four factors that traditionally constitute the preliminary

injunction calculus." City of Las Vegas v. Lujan, 891 F.2d

927, 931-32 (D.C. Cir. 1989). And of course we always accord

deference to the district court's findings of fact. See id. at

931. Here, however, the case can be resolved by reference to

purely legal claims about the FDA's decision, legal claims

that require deference not to the district court but to the

agency. See Novicki v. Cook, 946 F.2d 938, 941 (D.C. Cir.

1991).

Warner-Lambert's statutory claim is that the dosage form

definitions in the USP are binding upon the FDA under the

Food, Drug and Cosmetic Act and that under the USP's

definition, Mylan's product is a tablet. We assume in Warner-Lambert's favor that the USP definitions in question are

indeed binding on the FDA, but we do not see that the FDA

ruling here violates the key definition--that of capsules. The

USP defines them as "solid dosage forms in which the drug is

enclosed within either a hard or soft soluble container or

'shell.' " United States Pharmacopeia 1942 (1995). WarnerLambert identifies no characteristic of the Mylan product

that is inconsistent with this definition on its face. Rather it

relies on the declarations of two eminently distinguished

members of the USP's Committee on Revisions, in which both

argue that when read properly the USP definition precludes

such a finding. But as Warner-Lambert conceded at oral

argument, we owe these experts' interpretation no deference.

See Tr. of Oral Argument at 16. Of course the absence of an

administrative record explaining how the FDA applied the

terms "dosage form," "capsule," or "tablet" in this case also

deprives it of the deference that would ordinarily be due such

reasoning. See City of Kansas City v. HUD, 923 F.2d 188,

192 (D.C. Cir. 1991). But where the agency ruling seems

entirely congruent with the (allegedly) binding legal language,

the existence of a conflicting interpretation by others, no

matter how distinguished or well-informed about the background of the language, is an inadequate basis to overturn the

agency's ruling. Of course the opinions of Warner-Lambert's

experts would bolster Warner-Lambert's position if it had a

convincing claim that inconsistencies with earlier FDA deterUSCA Case #99-5048 Document #495826 Filed: 02/11/2000 Page 5 of 9
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minations rendered the FDA's decision arbitrary and capricious under the Administrative Procedure Act, 5 U.S.C.

s 706(2)(A). But, as we shall see, that is not the case.

The core of Warner-Lambert's inconsistency claim is that

the FDA has irrationally distinguished between virtually

identical products, "classifying Mylan's capsule-shaped tablet

in a gelatin shell as a 'capsule' while classifying gelatin-coated

capsule-shaped tablets as 'tablets.' " Appellant's Initial Br. at

19. Warner-Lambert does not claim that the FDA has ever

treated a capsule-shaped tablet in a gelatin shell as a tablet.

That is, it makes no claim of direct self-contradiction.

ANDA applications are not treated as adversary proceedings, and evidently no one in the process formally posed

Warner-Lambert's question as to why these superficially

rather similar things should be differently classified. As a

result the Mylan application file contains no explicit answer to

the question. In the preliminary injunction proceeding, however, the FDA offered materials as to prior decisions that

shed some light on the subject. For example, an FDA

response to a citizen petition filed on behalf of Novartis

Pharmaceuticals stated its position that "dosage form is the

way of identifying the drug in its physical form, which is

linked both to physical appearance of the drug product and to

the way it is administered." FDA Docket No. 96P-0459,

Nov. 2, 1998, Response to Petition filed by Novartis, Inc., at

12 (Nov. 2, 1998), Joint Appendix ("J.A.") 102, 113 (quoting

FDA Docket No. 93P-0421, Aug. 12, 1997, Response to

Petition filed by Pfizer, Inc., at 4). Similarly FDA responded

to such a petition by Zenith Goldline Pharmaceuticals, Inc.:

"The contents of a capsule do not change the fact that the

product is a capsule.... Compressed tablets with a gelatin

coating are considered by the Agency to be tablets." FDA

Docket No. OGD 98-045, Mar. 31, 1998, Response to Petition

filed by Zenith Goldline Pharmaceuticals, Inc., at 1, J.A. at

121.

These opinions support two inferences. First, they state

the general criteria that FDA says are properly applied in

making the "dosage form" determination--namely, that it is a

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matter of looking to a drug's (1) physical appearance and (2)

the way it is administered. Second, those general criteria are

consistent with the FDA's conduct here: Both products (Dilantin and the Mylan product) are administered orally,3 and

their physical appearance--a capsule shell with some contents--is the same. Warner-Lambert has not undertaken to

show that the Mylan product looks "more" like a gelatincoated tablet than it looks like what it is, a capsule with a

tablet inside.

Warner-Lambert argues that these rulings were not part

of the administrative record. True enough--but that hardly

renders them immaterial as evidence that the FDA has

formulated a principle and that its individual case decisions

have stuck to it. Indeed, at that level Warner-Lambert

really has no complaint.

Its real complaint, then, is that the line the FDA has drawn

is rather formalistic; so much so as to be in effect arbitrary

and capricious. Obviously drawing distinctions without a

difference may be arbitrary. See Independent Petroleum

Ass'n of Am. v. Babbitt, 92 F.3d 1248, 1258-60 (D.C. Cir.

1996); Green Country Mobilephone, Inc. v. FCC, 765 F.2d

235, 238 (D.C. Cir. 1985). But consider Warner-Lambert's

basic position. It rests on the statutory requirement that an

ANDA can be approved only if the new drug is identical in

"dosage form." Its attack on the FDA's line-drawing can be

framed in three ways: It may be saying that any line between

capsules and tablets is silly or pointless, in which case the two

dosage forms should be collapsed. If so, Warner-Lambert

cannot have been harmed here, as the dosage form would

plainly have been identical for both products under the alter-

__________

3. The scope of the "administration" part of the dosage form

definition remains unclear. FDA acknowledges that "method of

administration" is more subtle than simply distinguishing between

the manner in which the drug is introduced into the patient, such as

orally, topically, or via injection. But we have no occasion to probe

the contours of "method of administration" in this case because

there is no allegation that Dilantin and Mylan's product have

different methods of administration.

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native rule. Or Warner-Lambert may be saying that while

there should be a line between capsules and tablets, the

FDA's line is incapable of consistent application because

there is no method for separating a gelatin coating from a

capsule shell. But Warner-Lambert has provided no reason

to believe that the FDA is unable to distinguish consistently

between the two. Finally, Warner-Lambert may be saying

the FDA has drawn the line in the wrong place, that capsules

containing tablets belong with tablets rather than with capsules. Yet it offers virtually no reason to think that there is

anything irrational about the FDA's choice of exactly where

in these shadowlands it should locate this border (a necessary

border, under this last assumption).

The exception (the reason the previous sentence says "virtually no reason") is a claim tucked away in the section of

Warner-Lambert's brief devoted to USP definitions. It asserts that the way in which the body absorbs a garden-variety

capsule is different from the way it absorbs a tablet in a

capsule, so that the FDA's capsule classification of the Mylan

product may lead to inaccurate inferences about its absorption.

There are at least three difficulties with this claim. First,

Warner-Lambert made no attack on the FDA's bioequivalence finding. Bioequivalence requires an FDA finding that

"the rate and extent of absorption of the [new] drug do not

show a significant difference from the rate and extent of

absorption of the listed drug." 21 U.S.C. s 355(j)(8)(B).

Thus, contrary to what Warner-Lambert proposes here, we

must assume that rate and extent of absorption are the same.

Second, Warner-Lambert's argument would place limits on

the capsule dosage form that have no statutory or regulatory

basis. As Warner-Lambert acknowledges, Reply Br. at 9,

multiple tablets encapsulated in a shell are treated as capsules. Warner-Lambert evidently accepts this as sound

practice. But under Warner-Lambert's conception of dosage

form, a liquid-filled capsule (which Warner-Lambert agrees is

properly deemed a capsule) that sought to gain approval as a

generic equivalent of this tablet-filled capsule would have the

added hurdle of showing that the liquid would perform the

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same way as the tablets independent of a showing of bioequivalence. The FDA has not required such a showing. Third,

contrary to Warner-Lambert's assertion that bioequivalence

is insufficient because Mylan's product may have dangerous

lot-to-lot variation, the record contains graphs and other

materials purporting to demonstrate that Mylan's product is

at least as consistent as Dilantin, see J.A. 245-46 (depicting

lot-to-lot dissolution profiles for both products), and WarnerLambert makes no claim that the natural reading of these

graphs--namely that the profiles are identical--is in error.

Given the consistency of the FDA's classification of the

Mylan product with the language of the USP, with its stated

criteria for making dosage form classifications, and with its

specific dosage form classifications, there were no grounds for

granting the requested injunction. The decision of the district court is

Affirmed.

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