Warner Lambert Co v. Shalala, Donna E.

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

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 "Dilan-
tin."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 addi-
tional 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 injunc-
tion 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."

 * * *

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 there-
fore 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 equiva-
lence" which is based in part upon identity of dosage form. Phar-
maceutical 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 .

dispense a therapeutically equivalent generic alternative un-
less 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 applica-
tion. But Warner-Lambert rose quickly to the challenge.
Two weeks later it filed a complaint and request for prelimi-
nary 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 Phar-
macopoeia ("USP") for particular dosage forms as required
by the Food, Drug and Cosmetic Act (under which, Warner-
Lambert 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 deferen-
tial "clear error" or "abuse of discretion" standards, due to
the "latitude the district court properly enjoys in balancing

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 War-
ner-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). Warner-
Lambert 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 back-
ground 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 deter-

minations rendered the FDA's decision arbitrary and capri-
cious 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 proceed-
ings, 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, how-
ever, 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

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 (Di-
lantin and the Mylan product) are administered orally,3 and
their physical appearance--a capsule shell with some con-
tents--is the same. Warner-Lambert has not undertaken to
show that the Mylan product looks "more" like a gelatin-
coated 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.

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 cap-
sules. 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 "vir-
tually no reason") is a claim tucked away in the section of
Warner-Lambert's brief devoted to USP definitions. It as-
serts 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 absorp-
tion.

There are at least three difficulties with this claim. First,
Warner-Lambert made no attack on the FDA's bioequiva-
lence 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 cap-
sules. 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

same way as the tablets independent of a showing of bioequi-
valence. 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 Warner-
Lambert 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 dis-
trict court is

Affirmed.