Defendants' memo iso motion to stay

IN THE COURT OF COMMON PLEAS ROSS COUNTY, OHIO STATE OF OHIO ex rel MIKE DeWINE, ) CASE NO. CV-I7 Cl 000261 Ohio Attorney General, ) ) JUDGE SCOTT W. NUSBAUM Plaintiff, ) ) VJ.

) ORAL ARGUMENT REQUESTED

PURDUE PHARMA L.P., et al.

Defendants.

) ) ) )

MEMORANDUM IN SUPPORT OF DEFENDANTS’ MOTION TO STAY THIS CASE UNDER THE PRIMARY JURISDICTION DOCTRINE AND THE COURT’S INHERENT AUTHORITY TO STAY PROCEEDINGS

TABLE OF CONTENTS Page I.

PRELIMINARY STATEMENT

1

II.

BACKGROUND..................

,2

III.

ARGUMENT.............................

,7

A.

B. IV.

The Court Should Stay Any Remaining Claims Under The Primary Jmisdiction Doctrine And Its Inherent Authority To Control The Litigation Before It.......................................................................................

7

The Court Should Stay Any Remaining Claims In Deference To FDA’s Jurisdiction And The Pending FDA-Mandated Studies.................................

.9

CONCLUSION

18

1

TABLE OF AUTHORITIES Page Cases Aaromon v. Vital Pharmaceuticals, Inc., S.D.Cal., No. 09-CV-1333, 2010 WL 625337 (Feb. 17, 2010)......

8

Charvat v. EchoStar Satellite, LLC, 630 F.3d 459 (6th Cir. 2010).........................................

9

City of Chicago v. Purdue Pharma L.P., 211 F. Supp. 3d 1058 (N.D.I11.2016).............................

2

Endo Pharmaceuticals, Inc. v. Actavis, Inc., D.N.J., No. 12-CV-7591,2013 WL 4774494 (Sept. 3,2013).....

8

Gisvold V. Merck & Co., 62 F.Supp.3d 1198 (S.D.Cal.2014)....................................

8

Imagenetix, Inc. v. Frutarom USA, Inc., S.D.Cal., No. 12-OV-2823, 2013 WL 6419674 (Dec. 9, 2013)......

8

Kocolene Oil Corp. v. Ashland Oil, Inc., 509 F. Supp. 741 (S.D.Ohio 1981)................................

7, 9, 17, 18

Kovar v. Latosky, 11th Dist. Lake No. 2002-L-037,2003-0hio-1749.......

9

Landis v. N. Am. Co., 299 U.S.248 (1936).......................................................

9, 17, 18

Lazarus v. Ohio Cas. Group, 144 Ohio App.3d 716, 761 N.E.2d 649 (8th Dist. 2001)

7

Michael V. Ghee, 325 F.Supp.2d 829 (N.D.Ohio 2004).............................

9

People V. Purdue Pharma, Orange Cty. (Cal.) Sup. Ct. No. 201400725287, 2015 WL 5123273 (Aug. 27, 2015).... 1, 6, 16 Pacific Chem. Prods. Co. v. Teletronics Servs., Inc., 29 Ohio App.3d 45, 502 N.E.2d 669 (8th Dist. 1985),

7

Ramcharitar v. Procter & Gamble Co., S.D.Ohio, No. L15-CV-457, 2016 WL 796129 (March 1, 2016)..

7,8

State ex rel. Banc One Corp. v. Walker, 86 Ohio St.3d 169, 712 N.E.2d 742 (1999)................

7

State V. EPA, S.D.Ohio, No. 2:15-cv-2467, 2015 WL 5117699 (Sept. 1, 2015)

9

State V. Hochhausler, 76 Ohio St.3d 455, 668 N.E.2d 457 (1996)................

9

11

United States V. W. Pacific R.R. Co., 352 U.S. 59(1956).......................

7

Weinberger V. Bentex Pharm., Inc., 412 U.S. 645 (1973).....................

8, 17

Rules and Regulations 21 C.F.R. ยง 10.30(e)(1)....................

14

111

I.

PRELIMINARY STATEMENT The Ohio Attorney General, on behalf of the State of Ohio (“the State”), alleges that

Defendants* improperly and Ifaudulently promoted opioid pain medications by promoting them to treat “chronic pain.” Compl. % 4. As set forth in the concuiTently filed motions to dismiss, this view is inconsistent with the Food and Drug Administration’s (“FDA”) approval of opioid pain medications for just that purpose. And, as set forth in those motions, the Complaint fails to state a viable cause of action because, inter alia, the State’s claims are preempted by federal law.

If this Court does not dismiss the Complaint, FDA’s ongoing role in assessing the benefits and risks of opioid pain medicine nonetheless weighs strongly in favor of staying this case. To adjudicate allegations that Defendants misrepresented the risks and benefits of opioids, this Court will first be required to determine what the benefits and risks of opioid pain medications are. FDA, however, is in the process of examining that exact issue. It has ordered studies to further assess the benefits and risks of chronic opioid therapy, and those studies are currently underway.^ As another court recently found when staying a similar lawsuit filed by multiple California counties against many of the same opioid manufacturers as here, “FDA explored all the underlying issues involved in this lawsuit * * * and has taken action to further explore them.”

People V. Purdue Pharma, Orange Cty. (Cal.) Sup. Ct. No. 201400725287, 2015 WL 5123,213,

* The Defendants are Purdue Pharma L.P., Purdue Pharma Inc., and The Purdue Frederick Company, Inc. (“Pm-due”), Teva Pharmaceuticals Industries, Ltd., Teva Pharmaceuticals USA, Inc. (“Teva”), Cephalon Inc. (“Cephalon”), Johnson & Johnson, Janssen Pharmaceuticals, Inc., Ortho-McNeil-Janssen Pharmaceuticals, Inc., Janssen Pharmaceutica Inc. (“Janssen”), Endo Health Solutions Inc., and Endo Pharmaceuticals Inc. (“Endo”), Allergan Finance EEC f/l</a Actavis, Inc. f/k/a Watson Pharmaceuticals, Inc., Watson Laboratories, Inc., Actavis EEC, and Actavis Pharma, Inc.. Named defendant Allergan pic (which is not an opioid manufacturer) does not join in this motion because it is not subject to personal jurisdiction in this Court, but has filed a separate motion to dismiss. ^ The State’s claims will all necessarily fail if the FDA-ordered post-market studies confirm that Defendants did not misrepresent the relative risks and benefits of using opioids for long-term treatment of chronic non-cancer pain. But even if FDA later determines that the science does not support some of the challenged representations, the State would still need to establish that Defendants knew the representations were false when made. Thus, it is inefficient and potentially problematic for the Court to wade into this issue before the science is fully developed.

*2 (Aug. 27, 2015)^. Litigating medical and scientific issues that FDA has considered or i: considering “could lead to inconsistencies with the FDA’s findings, inconsistencies among the States, a lack of uniformity, and a potential chilling effect on the prescription of these drugs for those who need them most.” Id.

•

This action presents the same concerns:

the State alleges that Defendants “falsely

den[ied] or trivialize[d] the risks of opioids while overstating the benefits of using them for chronic pain”—an assertion that, in essence, asks this Court to determine what the public and doctors need to be told about these opioid medications. Compl. ^ 4. This is a complex question that is best left to FDA, the agency which is designated to address such issues and is actively examining the benefits and risks of long-term opioid therapy. A stay in favor of FDA’s primary jurisdiction is appropriate. It will allow FDA to complete its scientific evaluation, apply its medical and regulatory expertise, and address important and complex public health questions concerning the proper use of these medications."^ II.

BACKGROUND As discussed in Defendants’ joint motion to dismiss, FDA has determined that opioids

serve an important public health role: “When prescribed and used properly, opioids can effectively manage pain and alleviate suffering—clearly a public health priority. Chronic pain i: IS a serious and growing health problem: it ‘affects millions of Americans; contributes greatly to national rates of morbidity, mortality, and disability; and is rising in prevalence. ,»5 At the same In Purdue Pharma, the court ultimately lifted the stay for the limited purpose of allowing the defendants to submit additional demurrers challenging the sufficiency of the complaint.

Briefing is currently underway in the case. "‘in another lawsuit, an Illinois federal court declined to stay the matter under the primary jurisdietion doctrine. That court reasoned that it was “not being asked to adjudicate whether opioids are appropriate for the treatment of ehronic, non-cancer pain ... but whether defendants deliberately misrepresented the risks, benefits, and superiority of opioids when marketing them to treat „ , chronic pain, ‘contrary to . .. scientific evidence and their own labels. City of Chicago V. Purdue Pharma L.P., 211 F. Supp. 3d 1058, 1065 (N.D.I11.2016). However, the Illinois court did not explain how it could adjudicate the plaintiffs allegations without addressing the disputed scientific questions currently under FDA review.

955

^ See Ex. 1 (Sept. 10, 2013 Letter from FDA to PROP) at 2 & nn.4-6; see also Ex. 2 (July 25 2012 Letter from PROP to FDA).

2

, time, opioids pose signifieant risks—as disclosed on their FDA-approved labeling: “Opioids also have grave risks, the most well-known of which include addiction, overdose, and even death.

The labeling for these products contains prominent warnings about these risks. Moreover, the boxed warning states that all patients should be ‘routinely monitor[ed] * * * for signs of misuse, abuse, and addiction.

Ex. 1 at 2.

Recently, FDA explained why it decided to

“comprehensively review” these risks: Because protecting the public by ensuring the safety, efficacy, and quality of dmgs is an essential part of the FDA’s mission, it is appropriate to examine the agency’s actions in coping with the public health crisis of opioid misuse. As FDA leaders and as physicians, we believe that these efforts must be founded on two complementary principles: that the United States must deal aggressively with opioid misuse and addiction, and at the same time, that it must protect the well­ being ofpeople experiencing the devastating effects of acute or chronic pain. It is a d0icult balancing act, but we believe that the continuing escalation of the negative consequences of opioid use compels us to comprehensively review our portfolio of activities, reassess our strategy, and take aggressive actions when there is good reason to believe that doing so will make a positive difference.

Ex. 3 at 1 (emphasis added).

Recognizing the serious public health issue presented by opioid abuse and addiction, FDA has been actively monitoring and evaluating the risks and benefits of opioid pain relievers to ensure they are prescribed and used appropriately.

In July 2012, FDA approved a risk

evaluation and mitigation strategy (“REMS”) for ER/LA opioid analgesics that introduced safety measures to reduce risks of their use. The REMS, which FDA most recently updated in 2015, requires manufacturers to provide training for health care professionals on proper prescribing practices.® ® See Ex. 4 (Questions and Answers: FDA Approves a Risk Evaluation and Mitigation Strategy (REMS) for Extended-Release and Long-Acting (ER/LA) Opioid Analgesics); see generally Ex. 7 (Extended-Release (ER) and Long-Acting (LA) Opioid Analgesics Risk Evaluation and Mitigation Strategy (REMS)). FDA has also recently committed to “updating] [the] [REMS] requirements for opioids after considering advisory committee recommendations and review of existing requirements.” Ex. 8 at 1. A separate REMS has been adopted for the class of Transmucal Immediate Release Fentanyl (“TIRE”) opioids such as Cephalon’s Actiq and Fentora (the “TIRF REMS”). The TIRE REMS program similarly requires health care professionals to be trained on proper prescribing practices. Significantly, it also requires that prescribers enroll in an access program, review educational materials about each TIRF medicine, attest to understanding, among other things, the approved indication, contraindications, and appropriate dbsing for TIRF opioids, provide each patient with a medication guide for the TIRF medicine being prescribed, and complete and sign a TIRF REMS Access Patient-Prescriber 3

In July 2012, a group of physicians and public health officials called Physicians for Responsible Opioid Prescribing (“PROP”) filed a citizen’s petition (the “Petition”) with FDA, which, like the Complaint, claimed that the “[l]ong-term safety and effectiveness of managing [chronic non-cancer pain] with opioids has not been established.

Ex. 2 at 2. PROP asked that

FDA impose a “maximum duration of 90-days for continuous (daily) use for non-cancer pain.”

Id. In other words, PROP asked FDA to reverse or exclude approval for chronic pain as the State defines it;

non-cancer pain lasting three months or longer.” Compl. f 3 fh.l. PROP also asked

FDA to impose a daily dose maximum equivalent to 100 milligrams of morphine and “[sjtrike the term ‘moderate’ from the indication for non-cancer pain,

Ex. 2 at 2. FDA undertook a 14-

month-long review in which the agency held public hearings and workshops, received voluminous testimony and over 2,000 comments from experts and concerned eitizens,’ and comprehensively assessed the “relevant literature.” Ex. 1 at 6.

On completing that review, FDA coneluded that the scientific evidence did not support the restrictions PROP advocated and determined that opioids should continue to be available for the treatment of ehronie non-caneer pain. FDA rejeeted any distinction between using opioids for “cancer” versus “non-cancer” pain, id. at 6, 9, and it concluded, based on current evidence, that limiting the dose and duration of the use of opioids was not supportable, id. at 14. FDA did, however, direct certain labeling changes for Extended Release/Long Acting (“ER/LA”) opioids. 8 Agreement Form with each new patient before writing the first prescription for a TIRF medicine.

See Ex. 5 (Questions and Answers; FDA Approves a class Risk Evaluation and Mitigation Strategy (REMS) for transmucosol immediate-release fentanyl (TIRF) medicines); Ex. 6 (Transmucosol Immediate Release Fentanyl (TIRF) Risk Evaluation and Mitigation Strategy (REMS)).

FDA noted that “the majority of comments opposed PROP’S requests” and that “[mjany professional societies,” including the American Medical Association, “did not support the Petition and stated that the data cited by PROP did not support PROP’S requests.” Ex. 1 at 5.

8

Instead of replacing the terms “moderate to severe pain” with a categorical requirement of “severe pain,” as PROP had requested, FDA changed the indication in the labeling for ER/LA opioids to require pain “severe enough to require daily, around-the-clock, long-term opioid treatment, and for which alternative treatment options are inadequate.” Ex. 1 at 7-8. FDA chose to discontinue the “use of terminology predicated only on a categorical ‘severity scale’ {e.g., mild, moderate, severe) to characterize the intensity of pain for which ER/LA opioids are indicated” in favor of a “more thoughtful determination that [a patient’s] pain—however it may 4

Despite its rejection of the Petition’s attempt to eliminate the approval of opioids for the heatment of chronic non-cancer pain, FDA recognized that “additional action” might be warranted if relevant supporting data emerged.

Accordingly, FDA exercised its statutory

authority to order opioid manufacturers to conduct additional studies and clinical trials to further assess the “serious risks of misuse, abuse ^

^

addiction, overdose, and death associated with

the long-term use of opioid analgesics.” Ex. 1 at 10. Since responding to the Petition, FDA has reviewed and approved protocols for the mandated studies and committed to “[r]e-examin[ing] the risk-benefit paradigm for opioids” and “defeating] [the opioid abuse] epidemic through a science-based and continuously evolving approach.” Ex. 8 at 1, 2.

FDA’s evaluation of these issues continues. In May 2017, FDA announced that it was modifying its post-market study requirements for manufacturers of opioids that contain abuse deterrent properties. See Ex. 9 (“New Safety Measures Announced for Extended-release and Long-acting Opioids”).

FDA has also taken additional action where it deems such action

warranted. On July 10-11, 2017, FDA convened a public meeting entitled “Data and Methods for Evaluating the Impact of Opioid Formulations with Properties Designed to Deter Abuse in the Post-Market Setting: A Scientific Discussion of Present and Future Capabilities.” Ex. 10. In his opening address, FDA Commissioner Dr. Scott Gottlieb discussed several activities that are underway at FDA in connection with opioids, including “[a] second new action *

aimed at

ensuring the safe use of the abuse detement opioid analgesic formulations.” Ex. 11 at 3.^

be defined—is severe enough to require” the use of ER/LA opioids for indicated uses.

(Emphasis in original.) Id. at 7-8. FDA also recently granted Purdue’s petition to make safety labels for immediate release opioids more similar to those for ER/LA. Ex. 28. _ ^ See Ex. 11 at 3. (“We’re undertaking a new study to better understand prescriber beliefs and attitudes when it comes to these new opioid formulations. We want to know whether the perceptions about the attributes of these drugs match the clinical realities. In particular, we want to know whether we have the right nomenclature for describing the drug features that are expected to make opioids less prone to abuse. Among other steps, we’ll be surveying doctors to better assess how they perceive these terms, and understand the clinical understanding that’s been developing around the ADF products.”).

5

By the time they conelude, the FDA-mandated post-market studies are expected to “result in the most comprehensive data ever collected in the field of pain medicine.

Ex. 8 at 2

(emphasis added). Most importantly for purposes of this motion, the studies will gather and assess evidence relating to the very risks and benefits of long-term opioid use that the State claims Defendants misrepresented. For example (and as described further below), while the State fails to plead the details of any fraud, the Complaint identifies in conclusory fashion seven categories of alleged misrepresentations, including that Defendants misrepresented the risks of addiction. As set forth below, the post-market studies will address, among other things, these same risks. 10 In other words, the studies will shed light on whether the science supports the challenged representations. The Purdue Parma court found that a stay was appropriate because: This case is about determining what the public and doctors need[] to be told about opioids. That determination necessarily entails much more than determining issues of false and misleading marketing. Underlying every issue here, this case requires this court to become an expert in the field in which it has no expertise * * * The patients, potential patients, and the medical community deserve more.

2015 WL 5123273, at *l-*2 (emphasis added).

Like FDA, the Centers for Disease Control and Prevention (“CDC”) has recognized the need for more data about risks and benefits of long-term opioid use. Although it has no legal authority to regulate opioids, the CDC issued a “Guideline for Prescribing Opioids for Chronic

10

See Ex. 26 (Letter from FDA to opioid manufacturers). Attached as Exhibits 12 through 15 are protocols for four of the FDA-mandated studies. These protocols were finalized in 2015 before FDA issued its more expansive post-market requirements. The protocols, however, remain unchanged with the exception of the applicable study numbers. The protocol for Study 3033-1 (previously designated 2065-1), titled^ prospective investigation of the risks of opioid misuse, abuse, and addiction among patients treated with extended-release/long acting (EWLA) opioids for the treatment of chronic pain. Ex. 12, will hereinafter be referred to as “Study 1.”

The protocol for Study 3033-9 (previously designated 2065-4B), titled A survey study to evaluate the relation between doctor/pharmacy shopping and outcomes suggestive of misuse, abuse and/or diversion. Ex. 13, will hereinafter be referred to as “Study 9.” Study 3033-11 (previously designated 2065-5), titled A randomized, double-blind, placebo-controlled, clinical trial of structured opioid discontinuation versus continued opioid therapy in suboptimal and optimal responders to high-dose long-term opioid analgesic therapy for chronic pain. Ex. 14, will hereinafter be referred to as “Study 11.” The protocol for Study 3033-5 (previously designated 2065-2B), titled Validation of PRISM-5-Op, Measure of Addiction to Prescription Opioid Medication, Ex. 15, will hereinafter be refemed to as “Study 5.”

6

Pain” (the “CDC Prescriber Guideline”) in March 2016. In the Guideline, the GDC recognized that “clinical scientific evidence informing the recommendations is low in quality,” and therefore “more research is necessary to fill in critical evidence gaps.’ Ex. 16 at 34; see also id. at Table 1 (listing 22 of the 25 evidence enhies as having limitations”).

serious limitations” or “very serious

Reputable commentators have, however, noted critically that the CDC’s

methodology holds opioid research to a higher standard than studies of other pain therapies. Ex. 27.

III.

ARGUMENT A.

The Court Should Stay Any Remaining Claims Under The Primary Jurisdietion Doctrine And Its Inherent Authority To Control The Litigation Before It

The doctrine of primary jurisdiction *

is concerned with promoting proper

relationships between the courts and administrative agencies charged with particular regulatory duties.

United States v. W. Pacific R.R. Co., 352 U.S. 59, 63 (1956). The doctrine “applies

where a claim is originally cognizable in a court and enforcement of the claim requires the resolution of issues that have been placed within the special expertise of an administrative body.”

State ex rel. Banc One Corp. v. Walker, 86 Ohio St.3d 169, 171, 712 N.E.2d 742 (1999). “[I]f the use of administrative proceedings will contribute to a meaningful resolution of the lawsuit[,] * * * the trial court should defer any action until that determination is made by the agency.”

Lazarus v. Ohio Cas. Group, 144 Ohio App.3d 716, 722-23, 761 N.E.2d 649 (8th Dist. 2001); Banc One at 745; Kocolene Oil Corp. v. Ashland Oil, Inc., 509 F. Supp. 741, 743 (S.D.Ohio 1981). Given the expert and specialized knowledge of the agency at issue, “[t]he doctrine is grounded upon the necessity for administrative uniformity and the need for administrative skill found only in a body of experts capable of handling the intricate facts of a particular case.

Pacific Chem. Prods. Co. v. Teletronics Servs., Inc., 29 Ohio App.3d 45, 48, 502 N.E.2d 669 (8th Dist. 1985) (citations omitted).

“The doctrine is particularly applicable to a case such as this where an administrative 7

agency has exercised its primary jurisdiction and is conducting proceedings involving the same question as the Court.” Kocolene, 509 F. Supp. at 743 (citation omitted). The decision in Ramcharitar v. Procter & Gamble Co., S.D.Ohio No. l:15-cy-457, 2016 WL 796129 (March 1, 2016), is instructive. Plaintiffs claimed that defendant’s advertising for baby wipes was false and misleading because the wipes were not “flushable” as advertised.

Id. at *1.

The court

determined that a stay was appropriate, however, because the Federal Trade Commission (“FTC”) was already investigating the issue and considering the appropriate definition of “flushability” and “[a] robust management of the ‘flushable’ problem by the FTC, rather than by courts, could avoid urmecessary inconsistencies and controversies, helping manufacturers, retail vendors and consumers alike.” Id. (internal quotation omitted). Further, where, as here, multiple similar lawsuits were pending across the country, “the risk of inconsistent decisions [was]

H. ^

a

significant factor that warrant[ed] a stay” because “the FTC is better suited to protect consumers nationally.” Id. at *2-*3 (quotation marks and citations omitted).

The same concerns are implicated here. Congress has tasked FDA—and, counter to the State’s reliance on the CDC’s statements, only FDA—^with primary responsibility for “determinpng] whether a drug is generally recognized as safe and effective.” Weinberger v.

Bentex Fharm., Inc., 412 U.S. 645, 654 (1973).

The Supreme Court has explained why

deference to FDA is important; Evaluation of conflieting reports as to the reputation of drugs among experts in the field is not a matter well left to a court without chemical or medical background. The determination whether a drug is generally recognized as safe and effective * * * necessarily implieates complex chemieal and pharmacological considerations. Threshold questions within the peculiar expertise of an administrative agency are appropriately routed to the agency, while the court stays its hand.

Id. at 653-54 (deferring to primary jurisdiction of the FDA). Multiple courts have applied this principle to dismiss or stay claims under the primary jurisdiction doctrine. As the court in Gisvold V. Merck & Co. put it: Through this action. Plaintiff invites the Court to weigh in, find in her favor, and take action by requiring Merck to make a disclaimer and engage in corrective advertising. Exercising such jurisdiction over Plaintiffs claims presents 8

,

substantial risk of inconsistent rulings on issues presently pending before the FDA. The investigation of clinical benefits of drugs is particularly within the FDA’s initial decisionmaking domain, and is therefore not appropriate for adjudication before completion of the FDA’s own decisionmaking process.

62 F. Supp. 3d 1198, 1204 (S.D.Cal.2014) (emphasis added). 11 Separate and apart from the primary jurisdiction doctrine, it is well settled that “the power to stay proceedings is incidental to the power inherent in every court to control the disposition of the causes on its docket.” Landis v. N. Am. Co., 299 U.S. 248, 254 (1936); State v.

Hochhausler, 76 Ohio St.3d 455, 466, 668 N.E.2d 457 (1996); Kovar v. Latosky, 11th Dist. Lake No. 2002-L-037, 2003-Ohio-1749, ^ 15. Such a stay is appropriate in cases like this one, which are “of extraordinary public moment,” that directly affect “the public welfare,” and which present issues “great in their complexity [and] great in their significance.' Landis, 299 U.S. at 256; State v. EPA, S.D.Ohio No. 2:15-cv-2467, 2015 WL 5117699, *3 (Sept. 1, 2015). Whether a stay pursuant to the Court’s equitable powers is appropriate turns on “a weighing of the potentiality of another case having a dispositive etfect on the case to be stayed, the judieial economy to be saved by waiting on a dispositive decision, the publie welfare, and the hardship/prejudice to the party opposing the stay.

Michael v. Ghee, 325 F.Supp.2d 829, 832

(N.D.Ohio 2004) (citation omitted).

B.

The Court Should Stay Any Remaining Claims In Deference To FDA’s Jurisdiction And The Pending FDA-Mandated Studies

To determine whether the doctrine of primary jurisdiction applies, courts consider three central factors; (1) the “advance[ment of] regulatoiy uniformity;” (2) whether the “question [is] * * * within the agency’s discretion;” and (3) the benefits to be derived “from [the] technical or 11

See also Imagenetix, Lnc. v. Frutarom USA, Inc. S.D.Cal. No. 12-cv-2823, 2013 WL 6419674, *4 (Dec. 9, 2013) (stay proper where “underlying issue” in plaintiffs elaims involved “complex” considerations and “technical and scientific questions” “within the primary jurisdiction of the FDA”); Aaronson v. Vital Pharmaceuticals, Inc., S.D.Cal. No. 09-cv-1333, 2010 WL 625337, *2 (Feb. 17, 2010) (dismissing UCL and FAL claims asserting misrepresentations of produet safety and eoncealment of risks because “the[] issues are best suited for the FDA”); accord Endo Pharmaceuticals, Inc. v. Actavis, Inc., D.N.J. No. 12-cv7591, 2013 WL 4774494, *2 (Sept. 3, 2013) (dismissing claim “bound-up with determinations that can only be made by FDA”), vacated as moot, 3d Cir. No. 13-3981, 2014 WL 6844812 (Nov. 21, 2014) (application of primary jurisdiction moot after the FDA issued its determination”).

9

policy considerations within the agency’s * * * expertise.” Charvat v. EchoStar Satellite, LLC, 630 F.3d 459, 466 (6th Cir. 2010) (quotation marks and citations omitted). All three faetors favor a stay here pending the outcome of FDA’s inquiry (including additional regulation or enforcement guidance). See Kocolene, 509 F. Supp. at 743.

First, a stay would advance regulatory uniformity hy avoiding the prospect of a decision here that conflicts with FDA’s assessment of the underlying scientific issues that will be infonned by the results of the ongoing clinical studies.

The potential for conflicting

determinations are especially acute in light of similar suits cun'ently underway in at least twelve other states, all of which involve nearly identical allegations against many of the same Defendants. 12 Second, the complex scientifie issues that underlie all of the State’s claims concerning the risks and benefits of opioids for long-term use are squarely within FDA’s discretion as evidenced by the active interest and involvement the agency is taking in these issues and its request for further post-market studies.

Third, staying this action would enhance the Court’s decision-making in this case by allowing the Court to take advantage of FDA’s expertise.

Before litigating these complex

medical and pharmacological issues involving the long-term use of opioids, the Court should await FDA’s considered analysis of the forthcoming data.

Indeed, comparison of each pui-ported misrepresentation to the post-market study protocols demonstrates that (a) FDA has not yet resolved the complex issues underlying the State’s allegations; (b) nor has the CDC, which, despite the State’s reliance on the CDC Prescriber Guideline, has no regulatory authority here; and (c) this case could not be tried

12

_ The other suits are pending in New York, Mississippi, Illinois, California, New Hampshire, Missouri, Oklahoma, Tennessee, Arkansas, Oregon, South Carolina, and New Mexico. As discussed above, an Illinois federal court declined to stay one of the Illinois actions. See supra n.

3. All other actions are at the pleading stage, with motion to dismiss briefing (including on primary jurisdiction grounds) underway or pending.

10

without addressing issues about the accuracy and adequacy of risk-benefit information provided to prescribing physicians that are best left to FDA’s expertise.

1. Risk ofAddiction. The Complaint alleges that “Defendants deceptively trivialized and failed to disclose the risks of long-term opioid use, particulaidy the risk of addiction.” Compl. ^ 88; see also, e.g., id. at

87-108 (alleging that addiction risk was misrepresented as “low” and

“rmlikely”). To support its allegations, the State points to statements by the CDC and FDA that opioids cany a serious risk of addiction to support their allegations. Id. at

90-91. But, the

issue is not whether opioids have a risk of addiction—^this has been well-understood for more than a century (and Defendants have warned about that risk since its products were first approved by FDA). The issue is what those precise addiction-related risks are and whether Defendants misrepresented them.

See, e.g., Compl. Tf 89 (alleging that addiction risk was

misrepresented as “less likely,” and “rare and limited,” and that “opioids are rarely addictive”).

The post-market studies will assess those very risks.

For example, the “primary

objective” of Study 1 is to "'quantify the serious risks of misuse, abuse, and addiction associated with long-term use of opioid analgesics for management of chronic pain,” including "[e]stimat[ing] the incidence of ^ ^ ^ addiction * * * associated with long-term use of opioids for chronic pain.'

Ex. 12 at 5 (emphasis added); see also id. at 13. Additionally, Study 5 is

designed to establish and validate the "measure of addiction.

Id. Ex. 15 at 4 (“Valid

measurement is essential to developing an accurate knowledge base regarding addiction to extended release/long acting (ER/LA) prescription opioids prescribed for chronic pain.”) (emphasis added). The Court should not determine whether Defendants misrepresented opioids’ addiction-related risks before FDA finishes its study of the nature and extent of those risks.

2. Pseudoaddiction.

The State claims that Defendants concocted and promoted the

concept of “pseudoaddiction”—drug-seeking behavior that mimics true addiction occurring in patients receiving inadequate pain relief—to diminish concerns about addiction by falsely implying that this concept is substantiated by scientific evidence. See Compl.

94-96. These

allegations ignore that FDA has accepted the concept of pseudoaddiction. For example, the 11

FDA-approved OxyContin label describes drug-seeking behavior and tactics but also states that “[pjreoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.” Ex. 17 (OxyContin label) at § 9.2. FDA-approved labeling for other opioids also embodies this concept. See also Ex. 18 (Duragesic label) at § 9.2; Ex. 19 (Nucynta ER label) at § 9.2; Ex. 20 (Opana ER label) at § 9.2; Ex. 21 (Kadian label) at § 9.2.

Additionally, the FDA-approved protocol for Study 9 recognizes that “doctor/pharmacy shopping can reflect a clinical need based upon inadequate analgesia” (i.e., pseudoaddiction), Ex. 13 at 5, and that the study will “[ejvaluate the reasons patients go to more than one prescriber or more than one phamacy to obtain prescription opioids,” id. at 3, 7. The Court should therefore await the FDA’s guidance on Study 9 before evaluating whether Defendants misleadingly promoted the concept of pseudoaddiction.

3. Manageability of Addiction Risk. The State alleges that Defendants misrepresented that addiction can be effectively managed through the use of “screening tools, patient contracts, urine drug screens, and similar strategies.” Compl. % 97. The Complaint alleges that “there are no studies assessing the effectiveness of risk mitigation strategies,” and that the CDC Prescriber Guideline supports the State’s allegations.

Id. at | 98.

But, in fact, the CDC Prescriber

Guideline does not state that addiction risk cannot be managed or that screening tools and questionnaires do not work. On the contrary, the Guideline recommends the use of screening tools. Recommendation 8 states that clinicians should gather and assess “history of overdose [and] substance use disorder.

Ex. 16 at 16. Recommendation 9 advises “reviewing] the

patient’s history of controlled substance prescriptions” using state monitoring programs. Id. And, Recommendation 10 proposes that clinicians “should use urine drug testing before starting opioid therapy.” Id. The Complaint quotes these recommendations selectively, emphasizing CDC’s caution “not [to] overestimate the ability of [risk stratification tools] to rule out risks from long-term opioid therapy.” Id. at 28. But it ignores CDC’s actual practical advice, which is that “[s]ingle screening questions can be used,” and “[v]alidated screening tools used.” Id. 12

^

can also be

Moreover, the State ignores the fact that FDA expressly directs the use of these screening tools and other strategies to help mitigate opioid abuse. See Ex. 7 (REMS) at 11 (prescrihers should “[ujnderstand and appropriately use screening tools for addiction or abuse to help assess potential risks associated with chronic opioid therapy and to help manage patients using ER/LA opioid analgesics {e.g., structured interview tools)”). Further, in assessing addiction risk from long-term opioid therapy. Study 1 will “[ejvaluate and quantify other risk factors for misuse, abuse, and addiction associated with long-term use of opioids for chronic pain, including: *

H:

personal or family history of substance abuse [and] history of psychiatric illness.” Ex. 12 at 13.

The Court should not determine whether Defendants misrepresented the manageability of addiction risks before FDA finishes studying this issue.

4. Withdrawal.

The State alleges that Defendants falsely claimed that “opioid

dependence can easily be addressed by tapering and that opioid withdrawal is not a problem,” Compl. Tf 99; see also id. at

100-101, and that various statements in the CDC Prescriber

Guideline regarding opioid tapering support the State’s allegations.

Id. at % 101.

But

Defendants’ FDA-approved labeling acknowledges that physically dependent patients can be withdrawn safely from opioid treatment by gradually tapering the dosage.*^ And, the CDC Prescriber Guideline merely acknowledges additional data on opioid dosing strategies is needed, particularly on this issue. Ex. 16 at 10, 46. FDA has mandated additional studies and the Court should await its guidance. For example. Study 11 will assess the “efficacy of removal from opioid therapy.” Ex. 14 at 4, 34. A critical part of this study is to systematically analyze and measure the withdrawal symptoms of patients who receive long-term opioid treatment. See, e.g., id. at 52, 64, 71 (withdrawal symptoms to be measured by the Subjective Opiate Withdrawal Scale, the Clinical Opioid Withdrawal Scale, and “the occurrence of typical withdrawal AEs

- 13

See, e.g.. Ex. 17 at §§ 2.9, 9.2 (“When the patient no longer requires therapy * * *, taper the dosage gradually * * *. Healthcare providers should be aware that addiction may not be accompanied by concuiTent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.”).

13

[adverse events], including chills, sweating, hemor, and muscle cramps”). The Court should not assess the challenged representations without the benefit of this analysis.

5. Higher Doses. The State alleges that Defendants misrepresented that “doctors and patients could increase opioid dosages indefinitely without added risk and failed to disclose the greater risks to patients at higher dosages.” Compl. *1 102; see also id.

103-104. Yet again,

the State claims that the CDC Prescriber Guideline supports this claim. Id. f 104. Yet, the CDC’s statements are inconsirtent with FDA’s conclusions regarding the available data on highdose opioid therapy. In its Response to the PROP Petition, for instance, FDA denied a request to limit the dose of opioids, concluding “the available information does not demonstrate that the relationship [between opioid dose and risk of certain adverse events] is necessarily a causal one.

Ex. 1 at 12. As a result, FDA ordered post-market studies to assess this issue. Id. at 10-11.

Specifically, Study 1 will “[e]valuate and quantify other risk factors for misuse, abuse, and addiction associated with long-term use of opioids for chronic pain, including: * * * dose * =>= * of opioid use.” Ex. 12 at 5 (emphasis added). The Court should not assess the accuracy of the challenged representations without the benefit of FDA’s further evaluation, including its analysis of the results of the analysis that is eun-ently underway in Study 1.

Moreover, in August 2017, PROP filed a new petition again asking FDA to consider the risks and benefits of high-dose opioids. Ex. 22. FDA has an obligation to “rule upon” the new petition within 180 days, 21 C.F.R. § 10.30(e)(1), and in doing so may rely on hearings, conferenees, correspondence, or other investigatory tools, id. § 10.30(h). Here, the new petition bears remarkable resemblance to the Complaint’s allegations about high doses: the Complaint alleges that “the ‘benefits of high-dose opioids for chronic pain are not established’ while the ‘risks for serious harms * * * increase at higher opioid dosage,” including overdose risk, Compl.

Tf 103, and the new PROP petition similarly asserts that “[h]igher opioid dosages are associated with increased overdose risk * * * without neeessarily adding benefits for pain control or function.

Ex. 22. Study 1 and this new petition demonstrate that FDA is actively evaluating

this issue.

14

6. Abuse-Deterrent Formulations. The Complaint alleges that “Defendants’ deceptive marketing of the so-called abuse-deterrent properties of some of their opioids has created false impressions that these opioids can curb addiction and abuse.” Compl. f 105. According to the State, the CDC Prescriber Guideline establishes that abuse-deterrent properties do not fully prevent opioid abuse. Id. at f 107. This ignores that FDA-approved labels disclose that “abuse * H: H:

by the oral route, is still possible” for opioids ^designed to have abuse-deterrent properties and

remind that such foimulations remain “Schedule II controlled substance[s]” that “can be abused.” Ex. 17 at § 9.2. The allegations also ignore that FDA’s Opioid Action Plan includes “[e]xpanding access to abuse-deterrent foimulations (ADFs) to discourage abuse,” Ex. 23, and that FDA’s industry guidance instructs that “[o]ne potentially important step towards the goal of creating safer opioid analgesics has been the development of opioids that are formulated to deter abuse. FDA considers the development of these products a high public health priority.” Ex. 24.

Most recently, FDA’s Commissioner explained during two days of meetings the agency’s plan to “know whether the perceptions about the attributes of these drugs match the clinical realities,” including by “surveying doctors to better assess how they perceive” terms like “abuse-deterrent.”

Ex. 11. And, again. Study 1 will “[e]valuate and quantify other risk factors for misuse, abuse, and addiction associated with long-term use of opioids for chronic pain, including: * * ^whether or not product is abuse-deterrent ER/LA formulation.Ex. 14 at 5 (emphasis added). 14 7. Improvements and Benefits.

The Complaint alleges that “Defendants falsely and

misleadingly touted the benefits of long-term opioid use and falsely and misleadingly suggested that these benefits were supported by scientific evidence.” Compl. ^ 109. The State attempts to

14

Although the FDA recently requested that defendant Endo voluntarily remove its opioid product Opana ER from the market (a request to which Endo has agreed), that request was not related to the ongoing post-market studies that are examining the risks and benefits of long-term opioid therapy, nor is it based on concerns regarding the FDA’s prior approval of Opana ER and other opioids for the management of long-teim pain. Rather, the FDA requested voluntary withdrawal of Opana ER due to an observed increase in “injection abuse” by individuals misusing the formulation of that particular product leading to “a serious outbreak of HIV and hepatitis C, as well as cases of a serious blood disorder (thrombotic microangiopathy).”

See https ://www.fda. gov/NewsEvents/Newsroom/PressAnnouncements/ucm562401 .htm.

15

support this allegation with statements by FDA and the CDC that there is no “good evidenee” that opioids improve pain or function with long-tenn use. (Emphasis omitted.) Id. at f 111 (emphasis omitted). This allegation is contradicted by FDA’s recognition of the “numerous uncontrolled studies that have evaluated patients on opioids for as long as a year” and that “although some patients drop out of the studies over this period of time, many remain on opioid therapy, which may suggest that they continue to experience benefits that would warrant the risks of opioid use.

Ex. 1 at 10 n. 40; see also Ex. 27 at 1 (observing that duration of opioid

studies compares favorably with studies of other pain interventions and concluding that CDC’s dismissal of studies of less than a year is “inconsistent with current regulatoiy standards”).

Moreover, the post-market studies will examine the efficacy of opioids and provide further analysis about the degree to which they improve function. Specifically, Study 11 is designed to study a patient’s functioning on chronic opioid therapy, including assessing periodic changes in “physical function, impact of pain on function, pain quality, pain spread, neuropsychological function, sleep quality, mood, quality of life, and work productivity.

Ex.

14 at 15 (internal parentheticals omitted; emphasis added); see also id. at 63. Study 1 is also designed to collect and assess data regarding the “[hjealth and [functional [sjtatus” of patients on chronic opioid therapy. Ex. 12 at 8. These studies are thus examining certain issues the State claims Defendants deliberately misrepresented. As the Purdue Pharma court recognized, the Court should not deteimine whether the alleged representations are false or misleading before the FDA considers the results of these studies. 2015 WL 5123273, at *2 (“This action could lead to inconsistencies with the FDA’s findings *

^m

an area which is best left to agencies such as the

FDA who are designed to address such issues.”). 15 15

The Complaint also alleges that Purdue “misleadingly promoted OxyContin as being unique among opioids in providing 12 continuous hours of pain relief with one dose.” Compl. f 115-17 84. This allegation, however, has been previously addressed and rejected by FDA. In a January 2004 citizen petition, the Attorney General of Connecticut requested, among other things, labeling changes to OxyContin, asserting that OxyContin was not a true 12-hour drug and that using it on a more frequent dosing schedule increased its risk for diversion and abuse. FDA, however, denied the Attorney General’s petition in a response dated September 11, 2008, concluding that the evidenee failed to support the conclusion that using OxyContin more 16

In sum, the State asks the Court to ignore not only that FDA has largely rejected the claimed scientific basis for each of the seven categories of misrepresentations asserted in the Complaint, but also that FDA has ordered and approved protocols for additional studies for the express purpose of evaluating the scientific issues they present. At a minimum, the Complaint cannot be adjudicated without proper consideration of the underlying science and the “complex chemical and pharmacological considerations” involved in determining the relative risks and benefits of long-term opioid use—issues uniquely and appropriately within FDA’s primary jurisdiction. See Weinberger, 412 U.S. at 653-54. The State’s efforts are both premature and potentially counterproductive; they fail to “appropriately route[]” those fundamental scientific and medical evaluations in the first instance to FDA, the agency vested with authority and expertise over the matter, and, in doing so, they raise the specter of conflicting determinations of the important public health questions at issue. See id. at 654. Staying this action pending the outcome of FDA’s ongoing review and analysis of the underlying issues will preserve the rights of all parties and ensure that the scientific issues are properly and appropriately addressed by the expert agency charged with reviewing them for the country as a whole.

Moreover, separate and apart from the primary jurisdiction doctrine, the Court can and should exercise its inherent authority to stay this proceeding in the interest of justice. Landis, 299 U.S. at 254. The outcome of this case has the potential to harm thousands of Ohioans suffering from chronic pain and to create inconsistencies adversely affecting millions of these individuals across the country. FDA has determined that additional data should be gathered to aid it in its “difficult balancing acf ’ regarding the benefits and risks of long-term opioid use and has exercised its regulatory authority to order post-market studies addressing those very issues.

frequently than every 12 hours created greater risk. See Ex. 25 at 14-17. Indeed, FDA recently reaffirmed that OxyContin is approved only for 12-hour dosing. See Ex. 17 at 4, 30; see also id. at 39 (Medieation Guide insti'ucting patients to: “Take your prescribed dose every 12 hours at the same time every day. Do not take more than your prescribed dose in 12 hours. If you miss a dose, take your next dose at your usual time.”).

17

Because a determination of this case involves the same complex issues under evaluation in the ongoing post-market studies, the Court should have the benefit of appropriate input from regulatory and scientific experts before this case proceeds. See id. at 256.

Staying this case would also serve the sound policies pronounced in Landis by permitting the FDA-mandated studies to take their course and shine important additional light on scientific issues that are “great in their complexity, [and] great in their significance.” Landis, 299 U.S. at 256. The stay also provides an “economy of time and effort for [the Court], for counsel, and for litigants.” Landis, 299 U.S. at 254. Resolving this case would require this Court to make complex judgments that require input from FDA—all while FDA reviews the very same issues.

Because awaiting the outcome of the post-market studies will provide important scientific data for evaluating the challenged representations and avoid the risk of inconsistencies with the FDA findings, a stay continues to promote “the public welfare or convenience.” Landis, 299 U.S. at 256 (stay appropriate where agency action “may not settle every question of fact and law,” but will “in all likelihood * * * settle many and simplify them all.”).

IV.

CONCLUSION For the foregoing reasons, the Couit should stay any claims that remain in this case

pending the outcome of the FDA-ordered post-market studies.

18

DATED: September 8, 2017

Midi J. Buekley ((^3772), Trial Attorn -y /acob D. Mahle (00^797) ' Jeffrey A. Miller (0068815) VoRYS, Sater, Seymour and Pease LLP 301 East Fourth Sheet Suite 3500, Great Ameriean Tower Cincinnati, Ohio 45202 Tel: (513) 723-4002 Fax: (513) 852-7819 Sheila Bimbaum {pro hac application forthcoming) Mark S. Cheffo (pro hac application forthcoming) Hayden A. Coleman (pro hac application forthcoming) Quinn Emanuel Urquhart & Sullivan, LLP 51 Madison Avenue, 22"â&#x20AC;&#x2DC;^ Floor New York, New York 10010 Tel: (212) 849-7000 Fax: (212) 849-7100 Patrick J. Fitzgerald R. Ryan Stoll Skadden, Arps, Slate, Meagher & Flom LLP 155 North Wacker Drive, Suite 2700 Chicago, Illinois 60606 Tel: (312) 407-0700 Fax: (312) 407-0411 patrick.fitzgerald@skadden. com ryan.stoll@skadden.com Counsel for Defendants Purdue Pharma L.P., Purdue Pharma Inc., and The Purdue Frederick Company Inc.

DATED: September 8, 2017

By: John TUC R ELLIS LLP 950 Main Avenue Suite 1100 Cleveland, OH 44113-7213 Telephone: 216.592.5000 Facsimile: 216.592.5009 E-mail: j ohn.lewis@tuckerellis. com Charles C. Lifland (pro hac vice application pending) Oâ&#x20AC;&#x2122;MELVENY & MYERS LLP 400 S. Hope Street Los Angeles, CA 90071 Telephone: (213) 430-6000 Facsimile: (213) 430-6407 E-mail: clifland@omm.com Carolyn J. Kubota (pro hac vice application forthcoming) COVINGTON & BURLING LLP 1999 Avenue of the Stars Los Angeles, CA 90067 Telephone: (424) 332-4800 E-mail: ckubota@cov.com Attorneys for Defendants Janssen Pharmaceuticals, Inc., Johnson & Johnson, Janssen Pharmaceutica, Inc. n/k/a Janssen Pharmaceuticals, Inc., and Ortho-McNeil-Janssen Pharmaceuticals, Inc. n/k/a Janssen Pharmaceuticals, Inc.

DATED: September 8, 2017

Carole S. Rendon (0070345;, Trial Attorney Tera N. Coleman (0090544) BAKER & HOSTETLER LLP Key Tower 127 Public Square, Suite 2000 Cleveland, OH 44114-1214 (216) 696-0740 crendon@bakerlaw.com tcoleman@bakerlaw.com Ingo W. Sprie, Jr.*

ARNOLD & PORTER KAYE SCHOLER LLP 250 West 55th Street New York, NY 10019-9710 (212) 836-8000 Ingo.Sprie@apks.com

'

Attorneys for Defendants ENDO HEALTH SOLUTIONS INC. and ENDO PHARMACEUTICALS INC. * denotes national counsel seeking pro hac vice admission

DATED: September 8, 2017

Jo^ R. Mitchell (#0066759), Trial Attome^ ^Primary Responsibility from Thompson Hine LLP Stacey A. Greenwell (#0077909) THOMPSON HINE LLP 3900 Key Center 127 Public Square Cleveland, OH 44114-1291 Telephone: 216-566-5500 Facsimile: 216-566-5800 Stacev.GreenwelI@ThompsonHine.com John.Mitchell@ThompsonHine.com Donna Welch, P.C.* Martin L. Roth* Timothy Knapp* KIRKLAND & ELLIS LLP 300 North LaSalle Chicago, Illinois 60654 (312) 862-2000 donna.welch@kirkland.com martin.roth@kirkland. com timothy.knapp@kirkland. com Jeimifer G. Levy, P.C. * Jason R. Parish* KIRKLAND & ELLIS LLP 655 Fifteenth Street, NW Washington, DC 20005 p02) 879-5000 j ennifer.levy@kirkland.com jason.parish@kirkland.com Attorneys for Allergan Finance LLCf/k/aActavis, Inc.f/k/a Watson Pharmaceuticals, Inc. *Motions for Admission Pro Hac Vice to be filed

DATED: September 8, 2017

Of Counsel Steven A. Reed MORGAN, LEWIS & BOCKIUS LLP 1701 Market St. .

Philadelphia, PA 19103-2921 T: 215.963.5603 F: 215.963.5001 steven.reed@morganlewis.com Brian M. Ercole MORGAN, LEWIS & BOCKIUS LLP 200 South Biscayne Boulevard Suite 5300 Miami, FL 33131-2339 T: 305.415.3000 F: 305.415.3001 brian.ercole@morganlewis.com Tinos Diamantatos MORGAN, LEWIS & BOCKIUS LLP 77 West Wacker Drive Chicago, IL 60601-5094 T: 312.324.1000 F: 312.324.1001 tinos.diamantatos@morganlewis.com

By:.

Albert J. Lueas (0007676; Trial Attorney Jason J. Blalce (0087692) CALFEE, ELA.LTER & GRISWOLD LLP 1200 Huntington Center 41 South High Street Columbus, OH 43215 T: 614.621.1500 F: 614.621.0010 alueas@ealfee. com j blake(^calfee. com Georgia Yanchar (0071458) CALFEE, HALTER & GRISWOLD LLP The Calfee Building 1405 East Sixth Street Cleveland, OH 44114 T: 216.622.8200 F: 216.241.0816 gyanchar@calfee.com Attorneys for Defendants Cephalon, Inc., Teva Pharmaceutical Industries, Ltd., leva Pharmaceuticals USA, Inc., Watson Laboratories, Inc.,~ActavisLLC, andActavis Pharma, Inc. f/k/a Watson Pharma, Inc.

CERTIFICATE OF SERVICE I hereby eertify that on the 8“’ day of September, 2017, a true and aceurate eopy of the foregoing was served via electronic mail or U.S. Postal Service on the following parties: Mark H. Troutman Shawn Judge Gregory Travalio Isaac Wiles Burkholder & Teetor, LLC Two Miranova Place, Suite 700 Columbus, OH 43215-5098 mtroutman@isaacwiles.com sjudge@isaacwiles.com gtravalio@isaacwiles.com Special Counselfor the State of Ohio Steve W. Berman Emilee Sisco Hagens Berman Sobol Shapiro LLP 1918 Eighth Ave., Suite 3300 Seattle, WA 98101 steve@hbsslaw. com emilees(a),hbsslaw. com Jeimifer Fountain Connolly Hagens Berman Sobol Shapiro LLP 1701 Pennsylvania Ave. NW, Suite 300 Washington, D.C. 20006 ienniferc(a).hbsslaw. com Mike Moore Jonathan Compretta Mike Moore Law Firm, LLC P.O. Box 321048 Flowood, MS 39232 mm@mikemoorelawfirm. com fc(d),mikemoorelawfirm. com Jay Ward McGowan, Hood & Felder, LLC 321 Wingo Way, Suite 103 Mt. Pleasant, SC 29464 iward@mcgowanhood.com

Carole S. Rendon Tera N. Coleman Baker & Hostetler LLP 127 Public Square, Suite 2000 Cleveland, OH 44114-1214 crendon@bakerlaw. com tcoleman@bakerlaw. com Ingo W. Sprie, Jr.*

ARNOLD & PORTER KAYE SCHOLER LLP 250 West 55th Street New York, NY 10019-9710 (212) 836-8000 .

Ingo. Sprie@apks. com Counselfor Defendants Endo Health Solutions, Inc. and Endo Pharmaceuticals, Inc.

Albert J. Lucas Jason J. Blake CALFEE, HALTER & GRISWOLD LLP 1200 Huntington Center 41 South High Street Columbus, OH 43215 T: 614.621.1500 F: 614.621.0010 alucas@calfee. com jblake@calfee.com

Georgia Yanchar CALFEE, HALTER & GRISWOLD LLP The Calfee Building 1405 East Sixth Street Cleveland, OH 44114 T: 216.622.8200 F: 216.241.0816 gyanchar@calfee.com Steven A. Reed MORGAN, LEWIS & BOCKIUS LLP 1701 Market St. Philadelphia, PA 19103-2921 T: 215.963.5603 F: 215.963.5001 steven.reed@morganlewis. com

Brian M. Ercole MORGAN, LEWIS & BOCKIUS LLP 200 South Biscayne Boulevard Suite 5300 Miami, FL 33131-2339 T: 305.415.3000 F; 305.415.3001 brian.ercole@morganlewis.com Tinos Diamantatos MORGAN, LEWIS & BOCKIUS LLP 77 West Wacker Drive Chicago, IL 60601-5094 T: 312.324.1000 , F: 312.324.1001 tinos.diamantatos@morganlewis.com Attorneys for Defendants Cephalon, Inc., Teva Pharmaceutical Industries, Ltd, Leva Pharmaceuticals USA, Inc., Watson Laboratories, Inc., Actavis LLC, and Actavis Pharma, Inc. f/k/a Watson Pharma, Inc.

Carolyn J. Kubota COVINGTON & BURLING LLP 1999 Avenue of the Stars Los Angeles, CA 90067 ' Telephone: (424) 332-4800 E-mail: ckubota@cov.com

John Q. Lewis Tucker Ellis LLP 950 Main Avenue, Suite 1100 Cleveland, Ohio 44113 Email: iohn.lewis@tuckerellis.com Charles C. Lifland Oâ&#x20AC;&#x2122;Melveny & Myers LLP 400 South Hope St. Los Angeles, CA 90071 Tel: (213) 430-6000 Fax: (213) 430-6407 Email: clifland@omm.com Counselfor Johnson & Johnson, Janssen Pharmaceuticals, Inc, Ortho-McNeilJanssen Pharmaceituicals Inc. n/k/a Janssen Pharmaceuticals, Inc., and Janssen Pharmaceutica, Inc., n/k/a Janssen Pharmaceuticals, Inc. John R. Mitchell Stacey A. Greenwell THOMPSON HINE LLP 3900 Key Center 127 Public Square Cleveland, OH 44114-1291 Telephone: 216-566-5500 Facsimile: 216-566-5800 Stacey. Greenwell@,ThompsonHine.com John.Mitchell@ThompsonHine.com Donna Welch, P.C.* Martin L. Roth* Timothy Knapp* KIRKLAND & ELLIS LLP 300 North LaSalle Chicago, Illinois 60654 (312) 862-2000 donna. welch@kirkland. com martin.roth@kirkland.com timothy.knapp@kirkland.com

Jennifer G. Levy, P.C.* Jason R. Parish* KIRKLAND & ELLIS LLP 655 Fifteenth Street, NW Washington, DC 20005 (202) 879-5000 j ennifer.levy@kirkland. com jason.parish@kh-kland.com

Attorneys for Allergan Finance LLC f/Wa Actavis, Inc. f/k/a Watson Pharmaceuticals, Inc. John L. Davidson Davidson Bowie PLLC 2506 Lakeland Drive, Suite 501 Post Office Box 321405 Flowood, Mississippi 39232 ldavidson(a).dbslawfirm. net Of-Counselfor the State of Ohio

'aniel J. Buckley