Court Opinion

ID: 185085
Source: CourtListenerOpinion
Date Created: 2011-02-05 02:27:36+00
Date Added: 2024-06-11T17:26:13.051634
License: Public Domain

202 F.3d 326 (D.C. Cir. 2000)
Warner-Lambert Company, Appellantv.Donna E. Shalala, Secretary of Healthand Human Services, et al.,Appellees
No. 99-5048
United States Court of Appeals FOR THE DISTRICT OF COLUMBIA CIRCUIT
Argued September 17, 1999Decided February 11, 2000

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:

1
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.

2
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3
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. § 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. § 355(b).  Once the FDA approves the application  for the pioneer drug, it becomes a "listed drug," id.  § 355(j)(7), and generic copies may be approved using the far  simpler, abbreviated new drug application ("ANDA"), id.  § 355(j)(2)(A)(ii)-(iv).

4
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. § 355(j)(2)(A)(ii)-(iv),  (j)(4);  see also 21 CFR § 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. § 355(j)(2)(C); 21  CFR § 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. § 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) dispense a therapeutically equivalent generic alternative unless the doctor requires that the prescription be dispensed as  written.  See, e.g., N.Y. Educ. Law § 6816-a (McKinney  1999) (requiring generic drug substitution unless the doctor  indicates otherwise).

5
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.

6
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, 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.

7
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.

8
* * *

9
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 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).

10
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).  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 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 determinations rendered the FDA's decision arbitrary and capricious under the Administrative Procedure Act, 5 U.S.C.  § 706(2)(A).  But, as we shall see, that is not the case.

11
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.

12
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.

13
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 (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 gelatin coated tablet than it looks like what it is, a capsule with a  tablet inside.

14
Warner-Lambert argues that these rulings were not part  of the administrative record. True enough--but that hardly  renders them immaterial as evidence that theFDA has  formulated a principle and that its individual case decisions  have stuck to it.  Indeed, at that level Warner-Lambert  really has no complaint.

15
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 alternative 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 shadow lands it should locate this border (a necessary  border, under this last assumption).

16
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.

17
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. § 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  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 Warner Lambert makes no claim that the natural reading of these  graphs--namely that the profiles are identical--is in error.

18
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

19
Affirmed.

Notes:

*
 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."

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  § 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>.

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.