182 F.3d 975 (D.C. Cir. 1999)
Pfizer Inc.,Appellantv.Donna E. Shalala, Secretary, U.S. Department of Health and Human Services, et al.,Appellees
No. 98-5151
United States Court of AppealsFOR THE DISTRICT OF COLUMBIA CIRCUIT
Argued February 1, 1999Decided July 16, 1999

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
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:


1
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.


2
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.  § 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 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

3
The approval of the FDA is required before any drug may  be marketed in the United States.  See 21 U.S.C. § 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. § 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. § 355(j).


4
In order to gain approval of an ANDA, an applicant must  show that its generic drug is "bioequivalent to the listed  [pioneer] drug."  Id. § 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.  § 355(j)(8);  21 C.F.R. § 320.1(e).


5
To gain approval as a "pharmaceutical equivalent," 21  C.F.R. § 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.  § 355(j)(2)(A)(ii)-(iii);  see also id. § 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.  § 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. § 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.


6
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. § 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.  § 355(j)(4).


7
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

8
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.


9
In 1993 Pfizer filed a "citizen petition" with the FDA,  pursuant to 21 C.F.R. § 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."


10
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.


11
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.


12
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

13
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?


14
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 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)).


15
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).


16
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 180day marketing priority as against any later-filed generic  application.  See 21 C.F.R. § 314.107(c).  In other words, 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.


17
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."


18
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. § 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. § 355(j)(2)(A)(vii)(IV).  Nothing in the Act,  however, precludes the owner of a pioneer drug from waiting 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.


19
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.


20
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.  § 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 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").


21
* * *


22
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. § 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").


23
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).


24
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 U.S. 232, 242 (1980).

III. Conclusion

25
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 thereforeAffirmed in part and reversed in part.



Notes:


*
 Neither party claims there is any likelihood that the patent suit  will be dismissed or settled at an earlier date.


