MYLAN LABORATORIES LTD.; Mylan Pharmaceuticals, Inc., Plaintiffs, v. U.S. FOOD AND DRUG ADMINISTRATION, et al., Defendants, and Ranbaxy Laboratories Limited, Intervenor-Defendant.
Civil Action No. 12-1637 (JDB)
United States District Court, District of Columbia.
Dec. 27, 2012.
910 F. Supp. 2d 299
IV. CONCLUSION
For all of the foregoing reasons, the Court shall DENY Rush‘s [28/34] Motion to Vacate. Furthermore, no Certificate of Appealability shall issue from this Court. To the extent Rush intends to file an ap-peal, she must seek a Certificate of Ap-pealability from the United States Court of Appeals for the District of Columbia Cir-cuit in accordance with
Andrew E. Clark, U.S. Department of Justice, Washington, DC, for Intervenor-Defendant.
MEMORANDUM OPINION
JOHN D. BATES, District Judge.
On September 28, 2012, the Food and Drug Administration (“FDA“) decided that Ranbaxy Laboratories Limited (“Ran-baxy“) had not forfeited its eligibility for 180-day exclusivity to market generic val-sartan tablets. Because of this decision, plaintiffs Mylan Laboratories Limited and Mylan Pharmaceuticals, Inc. (“Mylan“) are blocked from marketing their generic val-sartan tablets. Mylan brings this action challenging FDA‘s decision under the Ad-ministrative Procedure Act (“APA“) and the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act“), as amended by the Medicare Modernization Act of 2003. Be-fore the Court are Mylan‘s motion for a preliminary injunction to set aside FDA‘s September 28, 2012 decision and to require FDA to grant final approval to Mylan‘s abbreviated new drug application, FDA‘s motion to dismiss under
I. Statutory and Regulatory Background
This is a dispute about the right to 180-day marketing exclusivity under the Hatch-Waxman Act, codified at
To gain FDA approval to market a new drug, a pharmaceutical company must sub-mit a new drug application (“NDA“) that must include, among other things, informa-tion on the drug‘s chemical composition, clinical trial results showing the drug‘s safety and effectiveness, a description of the methods of manufacturing the drug, and proposed labeling for the drug. See
Pursuant to the Hatch-Waxman Act, a pharmaceutical company seeking to mar-ket a generic version of an approved drug is not required to submit an NDA and hence can avoid conducting costly and time-consuming clinical trials to show safe-ty and effectiveness. See Mova Pharm. Corp. v. Shalala, 140 F.3d 1060, 1063 (D.C.Cir.1998). Instead, it can submit an abbreviated new drug application (“ANDA“) showing that the generic drug is “bioequivalent” to the approved drug and meets certain chemistry and labeling requirements. See
In addition, an ANDA must contain one of four certifications as to each Orange Booklisted patent claiming the approved drug or a method of using the approved drug. The four certifications are: (I) that there is no patent information; (II) that the patent has expired; (III) that the pat-ent is set to expire on a certain date (“paragraph III certification“); or (IV) that the patent is invalid or will not be infringed by the generic drug (“paragraph IV certification“).
The effect of a paragraph IV certifica-tion is more complex. By statute, making a paragraph IV certification constitutes an act of patent infringement. See
To incentivize generic manufacturers to risk exposing themselves to patent in-
The 180-day exclusivity period may be forfeited, however. In the Medicare Mod-ernization Act of 2003, Congress added to the Hatch-Waxman scheme six “forfeiture events“; if any one of these events occurs, a first applicant forfeits its entitlement to 180-day exclusivity. See
But-for causation is not required to meet this exception.
II. Factual and Procedural Background
On December 28, 2004, Ranbaxy filed an ANDA to market a generic version of val-sartan tablets (40 mg, 80 mg, 160 mg, and 320 mg), a hypertension drug currently marketed by Novartis Pharmaceuticals Corp. under the brand name Diovan.
Ranbaxy did not receive tentative ap-proval within 30 months, however. As of June 28, 2007, 30 months after Ranbaxy‘s ANDA was filed, bioequivalence had been found acceptable, but the elements of chemistry and labeling remained outstand-ing. Forfeiture Memo 5. Between the fil-ing of Ranbaxy‘s ANDA and the June 28, 2007 forfeiture date, there had been changes to the approval requirements for both labeling and chemistry. First, on November 22, 2006, FDA approved a label-ing supplement for Diovan that consisted of changes to three sections of the drug‘s labeling.
After reviewing Ranbaxy‘s chemistry amendments, FDA tentatively approved Ranbaxy‘s ANDA on October 25, 2007, nearly four months after the 30-month forfeiture date.
About a year later, on September 15, 2008, Mylan filed an ANDA to market a generic version of valsartan tablets. My-lan‘s Mot. for Prelim. Inj. [ECF 17] (“My-lan PI Mot.“), Declaration of Wayne Tal-ton [ECF 17-5] (“Talton Decl.“) ¶ 4. Like Ranbaxy‘s ANDA, Mylan‘s ANDA con-tained a paragraph III certification as to the ‘578 patent, a paragraph IV certifica-tion as to the ‘197 patent, and a section viii statement for the ‘990 patent.
On September 21, 2012, FDA made pub-lic its October 25, 2007 tentative approval letter to Ranbaxy. Talton Decl. ¶ 19. Then on September 28, FDA took three actions related to Ranbaxy‘s and Mylan‘s ANDAs. First, as set forth in a 12-page memorandum, FDA determined that Ran-baxy had not forfeited its eligibility for 180-day exclusivity because its efforts to comply with the USP monograph, and FDA‘s review thereof, “were a cause of” Ranbaxy‘s failure to obtain tentative ap-proval within 30 months. Forfeiture Memo 12. FDA therefore found it unnec-essary to determine whether the Novem-ber 22, 2006 labeling change was also a cause of the failure to obtain tentative approval.
FDA has carefully considered the argu-ments set forth in Mylan‘s three letters in determining that the ANDA sponsor [Ranbaxy] that is eligible for 180-day exclusivity has not forfeited its eligibili-ty. Due to the regulatory restriction on disclosure of information in an unap-proved ANDA, however, we cannot pro-vide you the basis on which the Agency determined that the first applicant for valsartan tablets has not forfeited its eligibility because that analysis rests on confidential information contained in that application. FDA appreciates the challenge this presents to you and other parties affected by a forfeiture analysis, but the Agency is nonetheless prohibited at this time from disclosing any addi-tional information regarding the forfei-ture decision.
Mylan PI Mot., Letter from Robert L. West, Deputy Dir., OGD, to William A. Rakoczy [ECF 17-10] 4 (Sept. 28, 2012) (footnote omitted).3
Mylan now stands ready to market its generic valsartan tablets but is prevented from doing so by Ranbaxy‘s continuing eligibility for 180-day exclusivity. Mylan filed an action in this Court on October 2, 2012, and moved for a preliminary injunc-tion two days later. FDA has moved to dismiss Mylan‘s complaint or, in the alter-native, for summary judgment. Ranbaxy intervened as a defendant under
STANDARD OF REVIEW
A plaintiff seeking a preliminary injunc-tion must show (1) a likelihood of success on the merits, (2) a likelihood of irrepara-ble harm in the absence of an injunction, (3) that the balance of equities tips in its favor, and (4) that an injunction is in the public interest. Winter v. Natural Res. Def. Council, Inc., 555 U.S. 7, 20 (2008). These four factors have historically been evaluated on a “sliding scale,” such that “an unusually
Ordinarily, a motion to dismiss under
In reviewing agency action under the APA, however, a district court “sits as an appellate tribunal” to decide questions of law based on the administrative record. See Marshall Cnty. Health Care Auth. v. Shalala, 988 F.2d 1221, 1222-23 (D.C.Cir.1993). As a result, the usual standards do not apply, and in this context “the legal questions raised by a 12(b)(6) motion and a motion for summary judgment are the same.” See
DISCUSSION
I. Mylan‘s Motion for a Preliminary In-junction
A. Likelihood of Success on the Merits
The probability of success on the merits is informed by the deferential stan-dard of review under the APA. FDA‘s no-forfeiture decision may be set aside if it is “arbitrary, capricious, an abuse of discre-tion, or otherwise not in accordance with law.” See
1. Lack of reasoned decisionmaking
FDA determined that (1) the May 1, 2007 publication of the USP monograph for valsartan constituted a change in the requirements for approval of Ranbaxy‘s ANDA, and (2) this change was a cause of Ranbaxy‘s failure to obtain tentative ap-proval by the 30-month forfeiture date. Forfeiture Memo 6, 12. Mylan does not challenge the determination that there was a change in the requirements for approval; it challenges only the causation determina-tion, and argues that FDA has given no rational or reasoned explanation for deter-mining that publication of the USP mono-graph caused the delay in tentative ap-proval. See 12/7/12 Tr. of Mot. Hr‘g 27. Thus, the question for this Court is wheth-er FDA‘s causation determination was based on reasoned decisionmaking. See Fox, 684 F.3d at 75.
In its September 28, 2012 decision, FDA explained that whether publication of or a change in a USP monograph has caused a failure to obtain tentative approval is “a very fact-specific question” involving “a number of potential factors.” Forfeiture Memo 11. These factors include, but are not limited to: (1) “whether the mono-graph change is in a proposed or final monograph,” (2) “the timing of any publi-cation of or change in a monograph in relation to a particular 30-month forfeiture date,” (3) “whether FDA requires compli-ance with the new/changed compendial standard [i.e., the USP],” (4) “whether the [FDCA] requires compliance with the new/ changed compendial standard,” (5) “the consistency of the new/changed mono-graph with pre-existing approval require-ments,” (6) “the nature and timing of the sponsor‘s efforts to comply with USP mo-nographs,” and (7) “[the nature and tim-ing] of FDA‘s review of such efforts.”
FDA explained the basis for its decision that there was causation and hence no forfeiture as follows:
a new USP monograph for the drug substance, Valsartan, became official. In response, Ranbaxy submitted a chem-istry amendment on June 26, 2007, two days before the 30-month forfeiture date, to revise its drug substance specifi-cations and test methods to comply with the monograph. Specifically, Ranbaxy proposed the following changes to its drug substance specifications and test methods:
Changes in drug substance specifica-tions:
- Requirement for identification test by IR test redefined to include USP reference standard
- Limits and requirements for Absor-bance test revised as per USP mono-graph
- Changes in related compounds in line with USP monograph
- Criteria of ‘Any other individual impurity’ has been redefined to ‘Any other individual impurity (Ex-cluding Valsartan related compound A)’
- Limits of ‘Isoleucine analog of Valsartan’ and ‘Any other individual impurity (Excluding Valsartan re-lated compound A)’ have been re-vised
- Chemical name of Valsartan relat-ed compound A, Valsartan related compound B and Valsartan related compound C has been updated in line with USP 30
- Additional note for ‘In-house lim-its’ incorporated for Valsartan re-lated compound A and Any other individual impurity (Excluding Val-sartan related compound A)
Changes in the drug substance test meth-ods:
- Requirement for the IR test rede-fined and method for absorbance in-corporated
- Method for ‘Related Compound A’ and ‘Assay’ updated in line with USP 30
- Parameter for sensitivity incorporat-ed under the method for particle size
- Limit of quantification and the origin for Valsartan related compound A in-corporated in line with validation.
Ranbaxy also provided copies of its revised drug substance specifications and test methods reflecting these changes. On July 2, 2007, FDA held a telephone confer-ence with Ranbaxy, during which the Agency asked the firm to provide data to show equivalence between Ranbaxy‘s in-house test methods and the USP methods. Ranbaxy responded with a chemistry amendment on July 5, 2007. The amend-ment was reviewed and the ANDA was tentatively approved on October 25, 2007. As noted above, in the tentative approval letter, FDA stated that the USP mono-graph constituted a change in the require-ments for approval, but the Agency did not make any determination as to whether the change caused Ranbaxy‘s failure to obtain tentative approval by the 30-month forfei-ture date.
Upon the foregoing, FDA concludes that publication of the official USP drug sub-stance monograph for valsartan with which Ranbaxy had to comply prior to approval constituted a change in the re-quirements for approval. FDA further concludes that Ranbaxy‘s effort to com-ply with this new requirement, and FDA‘s review of that effort, was a cause of Ranbaxy‘s failure to obtain tentative approval by the 30-month forfeiture date.
Mylan contends that FDA‘s decision lacks any reasoned explanation and states
Putting aside this factor for a moment, FDA‘s decision addressed the remaining six factors, albeit not in a formulaic recita-tion. First, FDA noted that the USP mo-nograph was not merely proposed but be-came “official,” i.e., final, on May 1, 2007 (factor 1). Second, FDA noted the timing of publication--“approximately two months prior to the 30-month forfeiture date” (factor 2). Third, FDA stated that Ranbaxy “had to” comply with the mono-graph, and indeed both FDA and the FDCA require compliance with official USP monographs (factors 3 and 4). See
Mylan argues, however, that the missing factor--the consistency of the USP mono-graph with pre-existing approval require-ments--is the critical factor, and that FDA‘s failure to discuss it renders its no-forfeiture decision arbitrary and capri-cious. See 12/7/12 Tr. 10-11. FDA re-sponds that this factor “isn‘t all that rele-vant” in this case, because before the May 1, 2007 publication of the USP monograph for valsartan, there were no standards set forth in a USP monograph or other official compendium.
The Court agrees with Mylan that this factor--the consistency of the monograph with pre-existing requirements--should be considered in the causation analysis. If this factor is not part of the analysis, and only the other factors need be considered, then the causation analysis approaches a bright-line test. Considering those factors alone, nearly any publication of a new,
Here, however, FDA‘s decision reveals that it was based on more than just the fact and timing of the monograph‘s publi-cation. The Forfeiture Memo discusses Ranbaxy‘s efforts to comply with the mo-nograph, listing the specific changes to drug substance specifications and test methods proposed by Ranbaxy. See For-feiture Memo 5-6. It is true, as Mylan points out, that FDA‘s summary of these proposed changes repeats verbatim the language used by Ranbaxy in its June 26, 2007 amendment to its ANDA. See 12/7/12 Tr. 13; Letter from Sean M. Russell, Sen-ior Regulatory Affairs Assoc., Ranbaxy, to OGD, FDA (June 26, 2007) [AR 18-21]. But the fact that FDA used Ranbaxy‘s own words to give an accurate description of the proposed changes does not mean that FDA failed to consider the substance of the changes in making its forfeiture determination. As noted in the Forfeiture Memo, upon review of Ranbaxy‘s amend-ment, FDA had a telephone conference with Ranbaxy, at which it asked Ranbaxy to provide data to show equivalence be-tween its in-house test methods and the USP methods. Forfeiture Memo 6. Ran-baxy gave FDA the data it asked for, and more than three months later FDA tenta-tively approved Ranbaxy‘s ANDA.
FDA‘s “path” to its conclusion on causa-tion is not difficult to decipher. Compare, e.g., Transcon. Gas Pipe Line Corp. v. FERC, 518 F.3d 916, 922 (D.C.Cir.2008) (“Here we can discern the Commission‘s path....“); with Dickson, 68 F.3d at 1405 (finding it “impossible to discern the Board‘s ‘path’ “). A new, final USP mono-graph was published; Ranbaxy made an initial effort to comply with the mono-graph; FDA then asked for more data; Ranbaxy gave FDA more data; and be-cause FDA had to review Ranbaxy‘s amendments and the additional data to ensure that Ranbaxy‘s drug substance specifications and test methods met the standards set forth in the new monograph, tentative approval was delayed. This con-nection between the specific facts and FDA‘s conclusion is apparent from the face of the Forfeiture Memo and is both logical and rational. See Fox, 684 F.3d at 75; Dickson, 68 F.3d at 1404-05. And on this technical subject of drug substance specifications and test methods, such as “the [infrared] test” and “the method for particle size,” the Court finds it particular-ly appropriate to defer to FDA‘s expertise. See Tripoli, 437 F.3d at 77; Forfeiture Memo 6.
Mylan, stressing the consistency-with-pre-existing-requirements factor, argues that a rational connection is lacking be-cause FDA asked for data to show equiva-lence between Ranbaxy‘s in-house test methods and the USP methods. Hence, Mylan‘s argument goes, “[i]f whatever Ranbaxy was doing was the same as what the monograph did,” it is unclear from FDA‘s decision how a change, if any, could have caused the delay in tentative approv-al. See 12/7/12 Tr. 14-15. But this misses the point that FDA and Ranbaxy have made. See 12/7/12 Tr. 34-35, 44. Before the USP monograph became official, Ran-baxy was not required to comply with any USP standards because none existed. Af-ter the monograph became official, Ran-baxy not only had to comply with the standards set forth in the USP monograph but also had to show FDA that it was in compliance. FDA would not have asked for data to show equivalence if it already had such data. So even if “whatever Ran-baxy was doing was the same as what the
Finally, the Court rejects Mylan‘s con-tention that the May 1, 2007 publication of the USP monograph could not have caused the delay in tentative approval because a proposed monograph almost identical to the final one had been published in Janu-ary-February 2006, some 14 months be-fore the 30-month forfeiture date. Ас-cording to Mylan, Ranbaxy knew that it would be required either to comply with the proposed monograph or to use an ac-ceptable alternative method. Mylan Supp‘l Mem. 6-7. To the contrary, howev-er, Ranbaxy was not required to comply with the January-February 2006 proposed monograph. In general, the FDCA and FDA require ANDA applicants to comply with official, final USP monographs, but not with proposed USP monographs. See
2. Contrary to congressional intent
Mylan also argues that FDA‘s decision was arbitrary and capricious because it frustrates the congressional policy under-lying the Hatch-Waxman Act. See Mylan Reply 10-12 (citing Barnett v. Weinberger, 818 F.2d 953, 964 (D.C.Cir.1987); Beaty, 853 F.Supp.2d at 41). The Court is not persuaded.
Citing this Court‘s decision in Hi-Tech Pharmacal Co. v. FDA (”Hi-Tech I“), My-lan states that the goal of the forfeiture provisions is to “‘ensure that the 180-day exclusivity period enjoyed by the first ge-
Mylan is correct that in enacting the Hatch-Waxman Act Congress sought to promote generic competition. However, Congress created the 180-day exclusivity period for that very purpose and included in the statute an express exception to for-feiture for delays in tentative approval caused by changes in approval require-ments beyond an ANDA applicant‘s con-trol. Stripping Ranbaxy of exclusivity where, as FDA has determined, its failure to obtain tentative approval was caused by a change in approval requirements would contravene congressional intent as ex-pressly stated in the exception. It also would deprive Ranbaxy of its anticipated reward for “stick[ing] out [its] neck[] (at the potential cost of a patent infringement suit)” by challenging Novartis‘s patent and, at least in theory, decrease the ex-pected returns from future generic chal-lenges to patents claiming brand drugs. See Teva, 595 F.3d at 1318.
Here, FDA has applied the tentative approval forfeiture provision and its excep-tion to the facts of this case as it sees them. Considering the purposes of not only the forfeiture provision, as Mylan does, but also the exception and the exclu-sivity incentive created by Congress, the Court will not set aside FDA‘s decision on the ground that it frustrates the congres-sional policy underlying Hatch-Waxman.7
3. Failure to actively pursue ANDA approval
Mylan‘s final argument in support of its likelihood of success on the merits is that
“It is a hard and fast rule of admin-istrative law, rooted in simple fairness, that issues not raised before an agency are waived and will not be considered by a court on review.” Nuclear Energy Inst., Inc. v. EPA, 373 F.3d 1251, 1297 (D.C.Cir. 2004) (per curiam). Despite having sent three separate letters to FDA on the issue of Ranbaxy‘s eligibility for exclusivity, My-lan did not argue to FDA that Ranbaxy was not actively pursuing approval of its ANDA. Because FDA has not had a chance to consider this new argument, this Court will not consider it in the first in-stance.9
Also, Mylan raised this argument for the first time in this Court in its reply memo-randum in support of its motion for a preliminary injunction and in opposition to FDA‘s and Ranbaxy‘s motions. Mylan did not so much as mention the pertinent reg-ulation,
To be entitled to preliminary in-junctive relief, a plaintiff must show injury that is certain, great, actual, and imminent. See Wis. Gas. Co. v. FERC, 758 F.2d 669, 674 (D.C.Cir.1985). In the D.C. Circuit, “mere economic loss” does not, in and of itself, constitute irreparable harm. Id. at 674-75 (internal quotation marks omitted). Monetary loss, even “irretrievable” mone-tary loss, may constitute irreparable harm only if it is “so severe as to cause extreme hardship to the business or threaten its very existence.” Hi-Tech I, 587 F.Supp.2d at 11 (internal quotation marks omitted); Gulf Oil Corp. v. Dep‘t of Ener-gy, 514 F.Supp. 1019, 1026 (D.D.C.1981); see also Wis. Gas., 758 F.2d at 675.
Mylan alleges that absent injunc-tive relief it will suffer substantial, “irre-trievable” financial losses, including a loss in first-year sales of up to $44.55 million, or “perhaps more.” Mylan PI Mot. 27-28. But this figure represents less than one percent of Mylan‘s annual revenues, fore-casted to be close to $7 billion this year. See FDA MTD 34 (citing Mylan‘s Form 10-K Annual Report, available at http://investor.mylan.com/secfiling.cfm?filingID=1193125-12-70508). Hence, even if the losses alleged were certain, which they are not, they are not “so severe as to cause extreme hardship to [Mylan‘s] business or threaten its very existence.” See Hi-Tech I, 587 F.Supp.2d at 11 (internal quotation marks omitted).
Mylan also claims that the harm it will suffer is not “merely economic” because it has a “statutory entitlement” to immediate final approval of its ANDA. Mylan PI Mot. 26-27. Although courts have held that a first applicant‘s loss of its statutory entitlement to the 180-day exclusivity pe-riod is irreparable because once lost “it cannot be recaptured,” that is not what Mylan stands to lose here. See, e.g., Apotex, Inc. v. FDA, No. 06-627, 2006 WL 1030151, at *17 (D.D.C. Apr. 19, 2006); see also Mylan, 856 F.Supp.2d at 216-17 (“Nor can Mylan‘s situation be compared to those of companies that stand to lose sole market exclusivity.“). Mylan con-tends that it stands to lose the “flip side” of exclusivity--that is, its entitlement to final approval “because there is not exclu-sivity, because it‘s been forfeited.” See 12/7/12 Tr. 24-25. But the so-called enti-tlement that Mylan claims here is not just the “flip side” of 180-day exclusivity. Congress provided for exclusivity to en-courage and reward the first generics to challenge patents for brand-name drugs. See
In short, the harm Mylan alleges--loss of actual sales, sales opportunities, long-term contracts, and other market advan-tages--is really just economic, and given Mylan‘s status as a leading generic manu-facturer and its already-large market pres-ence, the potential financial impact on My-lan‘s business is too small to support a
Because Mylan can show neither a likeli-hood of success on the merits nor a likeli-hood of irreparable harm, Mylan is not entitled to preliminary injunctive relief, and the Court need not address the two remaining factors. See Sherley, 644 F.3d at 393; Sierra Club, 825 F.Supp.2d at 148.
II. FDA‘s and Ranbaxy‘s Motions for Summary Judgment
The administrative record on Ranbaxy‘s failure to obtain tentative approval within 30 months is complete. Both FDA and Ranbaxy have filed summary judgment motions that are fully briefed. For the reasons stated in Part I.A., the Court con-cludes that, as a matter of law, FDA‘s September 28, 2012 no-forfeiture decision is supported by the administrative record and is not “arbitrary, capricious, an abuse of discretion, or otherwise not in accor-dance with law.” See
CONCLUSION
For the foregoing reasons, Mylan‘s mo-tion for a preliminary injunction will be denied, and FDA‘s and Ranbaxy‘s motions for summary judgment will be granted. A separate order accompanies this memoran-dum opinion.
Notes
And that‘s why-predominantly why that factor, the consistency of the new/changed monograph with pre-existing requirements is not--isn‘t all that relevant here. Because no matter what the pre-existing require-ments were, they weren‘t set forth in any USP monograph. They were things that FDA and Ranbaxy had agreed upon. I mean, essentially, Your Honor, you go back to what does [the] ANDA have to show to get approval? Well, you have to show that you‘re making the same drug in many re-spects as the RLD, as the innovative drug. So until there‘s a USP monograph, that‘s being governed by the drug companies sort of doping out, “[H]ow do I make this drug? What are the tests? What are the specs?” Submitting it to the FDA. FDA is saying, “Well, you‘re close, but we‘d like to see you do this test, do that test.” Those were the pre-existing requirements. 12/7/12 Tr. 35.
Second, Mylan argues that FDA‘s decision leads to absurd results. See Mylan Supp‘l Mem. 9-11. Mylan tries to fault FDA for not mentioning that the USP monograph for val-sartan was revised in May-June 2007, after it was published on May 1, and argues that FDA could not conclude that the May 1 publica-tion, but not the later revision, “caused” Ran-baxy‘s failure to obtain tentative approval within 30 months. As Mylan well knows, however, but-for causation is not required, so if the May 1 change was a cause of the delay, it would not matter whether a later change also contributed to the delay. See Forfeiture Memo 2. And FDA has not effectively reward-ed Ranbaxy with exclusivity for “sitting on its hands until just two days before the [tentative approval] deadline.” See Mylan Supp‘l Mem. 10-11. As discussed above, Ranbaxy was not required to comply with the USP monograph until May 1, 2007, and Mylan has not argued that a responsive amendment submitted with-in two months of a change shows a lack of diligence.
Here, moreover, even if judicial consider-ation were appropriate, Mylan would be hard-pressed to show that FDA acted arbitrarily and capriciously by not addressing an argu-ment based on a regulation it has never en-forced. See Advocates for Highway & Auto Safety v. Fed. Motor Carrier Safety Admin., 429 F.3d 1136, 1149-50 (D.C.Cir.2005); Mylan, 856 F.Supp.2d at 215; Buckingham v. Mabus, 772 F.Supp.2d 295, 300 (D.D.C.2011); see also 12/7/12 Tr. 38.