UNITED STATES COURT OF APPEALS FOR THE D.C. CIRCUIT


PFIZER INC

v.

SHALALA, DONNA E.


98-5151a

D.C. Cir. 1999


*	*	*


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 prod- uct 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


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


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 expen- sive 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.


The FDA first reviews an ANDA (whether submitted for  approval as a
pharmaceutical equivalent or as a pharmaceuti- cal alternative) in
order to determine whether it may be  "received," i.e., accepted for
processing, for which the stan- dard is that "the abbreviated
application is sufficiently com- plete 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
require- ments, then it must approve the ANDA. See 21 U.S.C.  s


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 Pro- cardia 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 gas- trointestinal 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."


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 extend- ed release mechanism than does Procardia


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, capri- cious, 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 there- fore 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 jurisdic- tion 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 


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 pre- vent 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 My- lan'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


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, 


says Pfizer, the agency's acceptance of Mylan's ANDA "af- fects the
legal rights of all subsequent applicants referencing  Procardia XLR."
We find this argument doubly unpersua- sive. 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 competi- tion," FDA approval for a
pharmaceutical equivalent to Pro- cardia 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 My- lan'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


longer than 45 days to sue for patent infringement. There- fore, Pfizer
voluntarily incurred the expense of preemptive  patent litigation in
order to get a substantial statutory bene- fit, 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 deny- ing Pfizer's citizen petition, the
FDA did not apply that  interpretation to a particular set of facts,
as it did in accept- ing 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 recog- nize 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


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


* * *


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 be- cause the
agency contemplates no additional substantive anal- ysis of Mylan's
application. See Regional Rail Reorganiza- tion 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 


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


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.