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In re Asacol Antitrust Litigation

United States District Court, D. Massachusetts

November 9, 2017

IN RE ASACOL ANTITRUST LITIGATION

          MEMORANDUM AND ORDER

          Denise J. Casper United States District Judge.

         I. Introduction

         This is a putative class action in which the Plaintiffs, members of a putative class of end-payor purchasers of certain pharmaceutical products, [1] allege that the Defendants, manufacturers of certain pharmaceutical products, engaged in exclusionary conduct impermissible under antitrust laws by pulling one product, Asacol 400mg, from the market at the same that it introduced a new product, Delzicol. For the reasons set forth below, the Court DENIES the parties' motions to exclude testimony, D. 426; D. 427; D. 428; D. 429; D. 430; D. 431; D. 444, provides the reasons for ALLOWING the Plaintiffs' motion for class certification under Fed.R.Civ.P. 23(b)(3), D. 380, as it ruled in D. 559, and DENIES the Defendants' motion for summary judgment, D. 445.

         II. Factual Background

         The following facts are taken from the parties' statements of material facts, D. 450; D. 509; D. 510; D. 545, and accompanying exhibits unless otherwise noted.

         A. Regulatory Background

         Prior to approving a product, the Food and Drug Administration (“FDA”) reviews a New Drug Application (“NDA”) to determine whether a proposed drug is safe and effective for its proposed uses. 21 U.S.C. § 355; D. 450 ¶ 195; D. 510 ¶ 195. Even after the FDA approves an NDA, the agency continues to monitor the safety of the drug and retains the authority to withdraw its approval if it finds that the drug is not safe or effective. 21 U.S.C. § 355(e); D. 450 ¶¶ 199-200; D. 510 ¶¶ 199-200.

         After an NDA has been approved, applicants who wish to manufacture a generic version of the approved drug may receive permission to do so by submitting an Abbreviated New Drug Application (“ANDA”). D. 450 ¶ 31; D. 510 ¶ 31. The FDA then determines whether the drug proposed in the ANDA is sufficiently “bioequivalent” to the drug that was already approved -termed the “reference listed drug.” D. 450 ¶ 31; D. 510 ¶ 31; D. 458-5 at 455. When a generic manufacturer submits an ANDA, it makes a filing to the FDA regarding the status of patents associated with the NDA of the reference listed drug. D. 450 ¶ 35; D. 510 ¶ 35. In that filing, the generic manufacturer must certify: (1) that the manufacturer of the reference-listed drug did not indicate to the FDA that there were any patents associated with the NDA of the reference listed drug; (2) that the patents associated with the NDA of the reference listed drug have expired; (3) that the patents associated with the NDA of the reference listed drug will expire before the generic manufacturer will begin marketing its product; or (4) that the patents associated with the NDA of the reference listed drug are invalid, unenforceable, or will not be infringed by the generic manufacturer. 21 U.S.C. § 355(j)(2)(A)(vii); D. 450 ¶ 35; D. 510 ¶ 35. A generic manufacturer certifying that it will not market the drug until the relevant patents expire is called a “Paragraph III certification, ” and certifying that the patents associated with the NDA are invalid, unenforceable, or will not be infringed by the generic manufacturer is called a “Paragraph IV certification.” D. 450 ¶ 35; D. 510 ¶ 35.

         Under certain circumstances, the first generic manufacturer who submits an ANDA with a Paragraph IV certification will be eligible for 180 days of market exclusivity, during which it is the only manufacturer authorized to market a generic version of the reference listed drug. D. 450 ¶ 38; D. 510 ¶ 38. Generic products typically gain market share from brand-name products by virtue of state laws that allow or require pharmacists to substitute a generic product for the reference listed drug that is sufficiently bioequivalent. D. 509 ¶¶ 60-62; D. 545 ¶¶ 60-62.

         The filer of an ANDA with a Paragraph IV certification must provide notice to the holder of the NDA of the reference listed drug, who may then choose to file suit in federal court asserting its patent rights against the ANDA filer. D. 450 ¶ 39. However, the filer of an ANDA with a Paragraph III certification need not provide the same notice. 21 U.S.C. § 355(b)(3)(A). The filing of an ANDA with a Paragraph III certification need not be public. D. 509 ¶ 279; D. 545 ¶ 279. The FDA does, however, publicly announce its tentative or final approval of an ANDA. D. 450 ¶ 41; D. 510 ¶ 41.

         B. The FDA Approves Asacol and Asacol HD for Ulcerative Colitis

         “Ulcerative colitis is a chronic inflammatory bowel disorder that typically causes bloody diarrhea, rectal urgency, tenesmus, and abdominal cramping.” D. 450 ¶ 1; D. 510 ¶ 1. The condition is cyclical, such that patients will experience periods of time without symptoms intermixed with periods of time with symptoms, termed “flares.” D. 450 ¶ 2; D. 510 ¶ 2. Due to the cyclical nature of the condition, patients may use one mode of treatment during flares and another mode of treatment continuously, even when the patient is not experiencing symptoms. D. 450 ¶ 3; D. 510 ¶ 3. The most common treatment for ulcerative colitis is a class of drugs containing the active ingredient mesalamine. D. 450 ¶ 4; D. 510 ¶ 4. Mesalamine, however, is ineffective at providing relief if it is released either too early or too late. D. 450 ¶ 6; D. 510 ¶ 6.

         Proctor and Gamble Pharmaceuticals Inc. (“P&G”) submitted an NDA to the FDA, requesting permission to sell a delayed-release oral tablet containing 400mg of mesalamine, sold under the brand name “Asacol” (“Asacol 400mg”). D. 450 ¶ 7; D. 510 ¶ 7. There were two patents associated with Asacol 400mg, both of which expired on July 30, 2013. D. 450 ¶ 11; D. 510 ¶ 11. The Asacol 400mg tablet contained an acrylic based delayed-release coating, such that the active ingredient is released in the colon. D. 450 ¶ 9; D. 510 ¶ 9. This coating contained a plasticizer known as dibutyl phthalate (“DBP”). D. 450 ¶ 47; D. 510 ¶ 47. The FDA approved this NDA on January 31, 1992. D. 450 ¶ 7; D. 510 ¶ 7.

         On May 29, 2008, the FDA approved a new NDA from P&G - this one for a 800mg, long-acting mesalamine tablet, to be sold under the brand name “Asacol HD.” D. 450 ¶ 12; D. 510 ¶ 12. Asacol HD differs from Asacol 400mg in two important ways: first, it is 800mg, instead of 400mg, D. 450 ¶ 13; D. 510 ¶ 13; and second, it has a dual-layer coating rather than a single-layer coating. D. 450 ¶ 14; D. 510 ¶ 14. The coating for Asacol HD when launched contained DBP, like the coating for Asacol 400mg. D. 450 ¶ 47; D. 510 ¶ 47. Asacol HD was launched on July 7, 2009. D. 450 ¶ 18; D. 510 ¶ 18. The patents associated with Asacol HD are due to expire on November 15, 2021. D. 509 ¶ 24; D. 545 ¶ 24.

         C. P&G and the FDA Discuss Removing DBP from Asacol and Asacol HD

         In March 2009, after the approval of Asacol HD but before its sale, the FDA held a teleconference with P&G regarding whether “P&G would consider removing DBP from Asacol 400mg.” D. 450 ¶ 21; D. 510 ¶ 21; D. 456-6 at 58-59. According to P&G, the FDA requested the teleconference with P&G because it was aware of the “potential health risks associated with exposure to DBP demonstrated in numerous studies” and wanted to “discuss the issue” with P&G. D. 456-6 at 58. It the teleconference, P&G indicated that it was having internal discussions about removing DBP. D. 456-6 at 59. The FDA asked about P&G's plan to remove DBP from the Asacol 400mg formulation, stating that the FDA felt “some urgency on this as the public is interested in removing this chemical from products, ” and indicated that the FDA was “suggesting DBPs should be replaced.” D. 456-6 at 59. The FDA indicated that its timetable on having a dialogue with P&G about DBP was “as fast as possible.” D. 456-6 at 60.

         On April 16, 2009, P&G sent a proposed plan to reformulate Asacol 400mg without DBP to the FDA. D. 450 ¶ 85; D. 510 ¶ 85. The proposed plan suggested that the FDA allow P&G to prove bioequivalence between the then-current version of Asacol 400mg and a reformulated version of Asacol 400mg without DBP through “in vitro dissolution testing.” D. 450 ¶ 86; D. 510 ¶ 86.

         The parties dispute the extent to which there actually was a concern at P&G regarding the premature release of mesalamine in the Asacol products caused by premature dissolution that might have informed P&G's aims in reformulating the Asacol products. Several years prior, in 2005, Asacol HD had been recalled in Canada due to dissolution testing problems, and as a result, P&G had developed “Quick Test” methods to identify batches of product with microfractures, which made the product susceptible to dissolution problems. D. 450 ¶¶ 73-74; D. 510 ¶¶ 73-74. At some point in 2009, P&G outlined the use of “soft handling” - avoiding putting physical stress on the tablets across the supply chain by, for example, minimizing drops - as a strategy. D. 450 ¶ 77; D. 510 ¶ 77; D. 456-2 at 4. In light of this strategy, it's not clear that P&G considered the problem of dissolution failures to be ongoing rather than solved by the soft handling approach. D. 456-2 at 4, 54.

         On April 23, 2009, the FDA held a meeting with P&G regarding Asacol HD. D. 450 ¶ 66; D. 510 ¶ 66; D. 456-3 at 4. According to P&G, it proposed to the FDA a change to the specifications for the dissolution rate (i.e., the rate set by the FDA for the percentage of tablets that opened at a particular pH) and the FDA was supportive of that change. D. 450 ¶ 72; D. 510 ¶ 72; D. 456-3 at 4. The specification for Asacol HD at that time required a dissolution rate of 1% at a pH of 6, and P&G was proposing to change the specification for the dissolution rate to 4%. D. 450 ¶ 72; D. 510 ¶ 72; D. 456-3 at 4. P&G requested this change to allow for “one tablet in the sample [to] fail, ” that is, prematurely release the active ingredient, “without failing the specification, ” even though P&G “[did] not have a history of failing the 1% spec on release testing.” D. 456-8 at 9. According to P&G, the FDA also expressed that reformulation of Asacol HD to remove DBP “needs to proceed with urgency.” D. 450 ¶ 66; D. 510 ¶ 66; D. 456-3 at 4. The FDA also stated that it wanted the reformulation of Asacol HD to remove DBP to “solve the current dissolution issue.” D. 450 ¶ 72; D. 510 ¶ 72; D. 456-3 at 4.

         There were further communications between the FDA and P&G on these matters. D. 450 ¶ 88; D. 510 ¶ 88; D. 456-2 at 81-83. By August 6, 2009, the FDA sent a letter to P&G rejecting P&G's proposed use of “in vitro dissolution testing” and instead requiring P&G to perform “in vitro methods (comparative dissolution)” to show bioequivalence between the then-currently marketed version of Asacol 400mg and the reformulated version of Asacol 400mg. D. 450 ¶ 89; D. 510 ¶ 89; D. 456-6 at 88. On August 24, 2009, the FDA conferred with P&G to discuss bioequivalence testing and indicated that it might consider an approach of “combined in vitro dissolution and PK study, ” but also stated that it was in “heavy discussion internally in regard to Division policy on reformulation changes.” D. 450 ¶¶ 94-98; D. 510 ¶¶ 94-98; D. 456-6 at 93.

         On October 12, 2009, P&G again discussed the subject of bioequivalence testing with the FDA and stated that Warner Chilcott (which by that point had agreed to purchase P&G's Asacol business) was “leaning towards clinical trials because [it] was ‘concerned about the impact on the global business as well as lowering the bar for generics.'” D. 450 ¶ 99; D. 510 ¶ 99.

         An October 20, 2009 Technical Report indicated that P&G tested two compounds, dibutyl sebacate (“DBS”) and triethyl citrate (“TEC”) as potential replacements for Asacol 400mg and Asacol HD. D. 450 ¶ 87; D. 510 ¶ 87; D. 456-8 at 16. The Technical Report concluded that DBS was the “best match to the current DBP containing formulation.” D. 456-8 at 16.

         D. Warner Chilcott Purchases the Asacol Products

         On October 30, 2009, Warner Chilcott purchased P&G's portfolio of pharmaceutical products, including Asacol 400mg and Asacol HD. D. 450 ¶¶ 19-20; D. 510 ¶¶ 19-20. Warner Chilcott was concerned about the impending expiration of the patent for Asacol 400mg, but appeared to believe that it could manage that risk through product improvement including the recent launch of Asacol HD. D. 509 ¶¶ 148-155; D. 545 ¶¶ 148-155. The efforts of P&G and Warner Chilcott to convert patients from Asacol 400mg, which would lose patent protection in 2013, to Asacol HD, which would not lose patent protection until 2021, met with only limited success. D. 509 ¶¶ 156-159; D. 545 ¶¶ 156-159. By 2011, only approximately 22% of Asacol 400mg prescriptions transitioned to Asacol HD, which was far short of Warner Chilcott's internal projections. D. 509 ¶ 167; D. 545 ¶ 167.

         At the time of the purchase, Warner Chilcott was also aware of P&G's discussions with the FDA about the reformulation of Asacol 400mg and Asacol HD to replace DBP. D. 450 ¶ 22; D. 510 ¶ 22. There is a dispute between the parties over whether P&G conveyed any specific concerns it may have had regarding the performance of the DBP-containing coating of Asacol 400mg and Asacol HD to Warner Chilcott. Compare D. 450 ¶¶ 24-26 with D. 510 ¶¶ 24-26.

         E. Warner Chilcott Negotiates Bioequivalence Testing with the FDA

         Warner Chilcott proceeded with the discussions P&G had been having with the FDA over the bioequivalence testing for the reformulation of Asacol 400mg to remove DBP. By November 24, 2009, Warner Chilcott had submitted a draft protocol for a clinical end point study to establish bioequivalence to the FDA. D. 450 ¶ 101; D. 510 ¶ 101. On January 21, 2010, the FDA responded to Warner Chilcott's draft protocol with an Advice Letter. D. 450 ¶ 106; D. 510 ¶ 106. On February 22, 2010, Warner Chilcott filed a citizen petition with the FDA requesting that the “requirements for establishing bioequivalence for any reference listed delayed-release mesalamine tablet include: a clinical efficacy endpoint study; comparative [PK] testing under fed and fasted conditions; and rigorous in vitro dissolution testing, ” and that the FDA promulgate official guidance to that effect. D. 450 ¶¶ 108-09; D. 510 ¶¶ 108-09. On April 22, 2010, the FDA communicated that “it will be acceptable to establish bioequivalence through special dissolution and PK studies, ” but that “if PK and dissolution testing results are not convincing, then a clinical trial may be necessary to establish equivalence based on clinical end points.” D. 450 ¶¶ 113-14; D. 510 ¶¶ 113-14.

         The FDA's May 20, 2010 response to Warner Chilcott's citizen petition stated that the “FDA continues to recommend in vitro dissolution testing but now recommends comparative PK studies rather than comparative clinical endpoint studies to show bioequivalence for these products.” D. 456 at 3. It acknowledged that this presented a departure from its 2007 position that “comparative clinical endpoint studies, rather than PK studies, should be used (along with in vitro dissolution studies) to show bioequivalence in orally administered extended or delayed release mesalamine drugs.” D. 456 at 8. It attributed the change to “new data from PK and comparative clinical endpoint studies in modified release mesalamine products as well as recent developments in regulatory science concerning analysis of PK data.” D. 456 at 9. The FDA denied the request to publish guidance regarding bioequivalence testing. D. 450 ¶ 130; D. 510 ¶ 130.

         F. Warner Chilcott Shifts to a Capsule Formulation of Mesalamine (Delzicol)

         Contemporaneous with discussions with the FDA on bioequivalence testing, Warner Chilcott began to consider a potential “new product” that would be different from Asacol 400mg in more ways than just removing DBP. D. 509 ¶ 114; D. 513-46 at 2-3; D. 545 ¶ 114. By October 2010, Warner Chilcott was pursuing a “capsule containing 400mg of mesalamine, ” “compressed into four 100-mg mini-tablets encapsulated into a standard gelatin capsule.” D. 450 ¶ 131; D. 510 ¶ 131.

         On November 2, 2010 Warner Chilcott conferred again with the FDA about bioequivalence testing for the reformulation of Asacol 400mg. D. 450 ¶ 132; D. 510 ¶ 132; D. 456-7 at 12. In addition to discussing specific testing protocols, Warner Chilcott also informed the FDA that it was “considering possible reformulation of Asacol 400-mg tablets to . . . a capsule formulation.” D. 450 ¶ 133; D. 510 ¶ 133.

         In early 2011, Warner Chilcott worked on the proposed capsule formulation for testing, with the goal of having a batch prepared by July 1, 2011. D. 450 ¶ 138; D. 510 ¶ 138. By June 2011, management had confirmed that the prior “DBP replacement project” was “on-hold” because the plan was now “to focus on the Asacol LCM [life-cycle management] projects” including the capsule project. D. 509 ¶ 118; D. 513-45 at 2; D. 545 ¶ 118. By mid-June 2011, it was determined that the capsules had higher water levels than expected, which could jeopardize the July 1, 2011 production date. D. 450 ¶ 139; D. 510 ¶ 139; D. 456-11 at 8. By August 2011, Warner Chilcott planned to proceed with one 400-mg DBS tablet in a capsule instead of four 100-mg tablets.” D. 450 ¶ 140; D. 510 ¶ 140. By August 2011, Warner Chilcott appeared to be concerned that “Asacol 400 capsule[s] would not be bioequivalent to current Asacol 400 have shifted focus to new format” such that Warner Chilcott's product could “be a moving target for generics to delay their entry” and “gain time to further modify the coating for true patent protection.” D. 509 ¶ 188; D. 514-34; D. 545 ¶ 188.

         On October 21, 2011, Warner Chilcott submitted an amended protocol to the FDA, which stated, among other things, that Warner Chilcott was going to submit a capsule formulation, with a single 400-mg tablet, and without DBP, for bioequivalence testing. D. 450 ¶ 143; D. 510 ¶ 143. In that same document, Warner Chilcott stated that the tablet was encapsulated in a “hydroxypropyl methylcellulose (HPMC) capsule to provide a protective layer to maintain the integrity of the delayed-release coating under the mechanical stresses of handling and packaging. This capsule layer will dissolve earlier in the gastrointestinal (GI) tract and will not interfere with the delayed release mechanism.” D. 450 ¶ 144; D. 510 ¶ 144; D. 456-9 at 6. Between that point and March 2, 2012, the FDA and Warner Chilcott communicated regarding the specifications of the bioequivalence testing that would necessary. D. 450 ¶¶ 145-150; D. 510 ¶¶ 145-150. Ultimately, on June 13, 2012, the FDA agreed that Warner Chilcott had satisfactorily shown bioequivalence. D. 450 ¶ 157; D. 510 ¶ 157.

         Notwithstanding a delay in obtaining validated experimental data to support Warner Chilcott's hypothesis regarding the relative stability of the capsule, D. 509 ¶¶ 199-213; D. 545 ¶¶ 199-213, on July 30, 2012, Warner Chilcott submitted an NDA to the FDA for the 400mg mesalamine delayed release single tablet in a capsule, without DBP, which was later sold under the name Delzicol. D. 450 ¶¶ 51-52; D. 510 ¶¶ 51-52. Warner Chilcott requested an expedited “6 month priority review” from the FDA on the NDA for Delzicol on the grounds that the FDA had expressed a safety concern with DBP, which was granted. D. 450 ¶ 53; D. 510 ¶ 53. On February 1, 2013, the FDA approved the NDA for Delzicol. D. 450 ¶ 54; D. 510 ¶ 54. In approving the label for Delzicol, the FDA recommended a removal of certain warning language regarding DBP. D. 450 ¶¶ 173-176; D. 510 ¶¶ 173-176.

         G. Warner Chilcott Launches Delzicol, Pulls Asacol, and Shifts to a Patented Capsule for Delzicol

         On March 18, 2013, Warner Chilcott launched Delzicol. D. 450 ¶ 55; D. 510 ¶ 55. On the same date that Warner Chilcott launched Delzicol, Warner Chilcott stopped selling and marketing Asacol 400mg. D. 450 ¶ 57; D. 510 ¶ 57. The “hard switch” - that is, pulling Asacol 400mg from the market once Delzicol was launched - meant that patients who had been taking Asacol 400mg no longer had the option of continuing with that product - they had to choose between switching to Delzicol, switching to Asacol HD (which was still on the market but had a different dosage), or switching to a different product. D. 509 ¶ 79; D. 545 ¶ 79.

         In an earnings call in February 2013, Roger Boissonneault, the chief executive of Warner Chilcott, explained that the result of pulling Asacol 400mg from the market at the same time as the Delzicol launch would be that “the generic company doesn't even get launched because the reference product will be Delzicol.” D. 509 ¶ 71; D. 545 ¶ 71. “There won't be any Asacol out there. We've seen that happen with Doryx [another Warner Chilcott product], when the generic company got the product approved and, by that time, the product had moved on.” D. 509 ¶ 71; D. 545 ¶ 71.

         When Warner Chilcott pulled Asacol 400mg from the market, sales of Asacol 400mg and of the Asacol-branded products as a whole declined. D. 509 ¶¶ 331-32; D. 545 ¶¶ 331-32. There is a dispute between the parties regarding whether the sales of oral mesalamine drugs generally declined. D. 509 ¶ 333; D. 545 ¶ 333.

         When Delzicol first launched, the capsule on the tablet was an unpatented design. 450 ¶ 178; D. 510 ¶ 178. On March 12, 2013, Warner Chilcott submitted a supplemental NDA to the FDA requesting permission to use a patented capsule, termed the “Qualicaps capsule” for Delzicol. There is a dispute between the parties regarding whether Warner Chilcott experienced any cost savings as a result of the switch to the Qualicaps capsule. D. 450 ¶ 182; D. 510 ¶ 182. The FDA approved the NDA for the Qualicaps capsule on July 9, 2013. D. 450 ¶ 180; D. 510 ¶ 180. Warner Chilcott represented to the FDA that it had begun manufacturing Delzicol with the Qualicaps capsule in August 2013, but as of March 7, 2014, it had not yet begun selling Delzicol with the Qualicaps capsule. D. 450 ¶ 181; D. 510 ¶ 181.

         By 2015, Warner Chilcott introduced a 4x100mg formulation for Delzicol which was approved for pediatric use, and allows patients to open the capsule to swallow the 100mg tablets, allowing for flexible dosing. D. 450 ¶¶ 331-34; D. 510 ¶¶ 331-34.

         H, Subsequent Conduct by the Defendants

         Unlike for Asacol 400mg, Warner Chilcott's removal of DBP from the Asacol HD formulation was not accompanied by other changes. Warner Chilcott filed a supplementary NDA to the FDA regarding the new, DBP-free formulation of Asacol HD on September 24, 2015. D. 509 ¶ 125; D. 545 ¶ 125. The reformulation of Asacol HD did not go through expedited review. D. 509 ¶ 125; D. 545 ¶ 125. Asacol HD contained no less DBP than Asacol 400mg; in fact, it contained twice as much DBP per tablet. D. 509 ¶ 125; D. 545 ¶ 125. The FDA approved the supplementary NDA on May 5, 2016. D. 509 ¶ 125; D. 545 ¶ 125. In the United Kingdom, Allergan, Warner Chilcott's successor, launched a version of Asacol 400mg without DBP but also without a capsule. D. 509 ¶ 228; D. 545 ¶ 228.

         On October 1, 2013, Actavis PLC, which is now known as Allergan PLC, acquired Warner Chilcott, including the Asacol line of products. D. 509 ¶ 9; D. 545 ¶ 9.

         I. FDA Policy Regarding DBP Generally

         The FDA maintained a policy of encouraging manufacturers to discontinue the use of DBP and to require clearer warnings regarding the risks of DBP, but did not prohibit the use of DBP. In 2009, the FDA requested a revision to the label of Asacol 400mg and Asacol HD to provide information on the “effects of DBP in animals and humans.” D. 450 ¶ 111; D. 510 ¶ 111. Warner Chilcott released an updated label containing that information in May 2010. D. 450 ¶ 112; D. 510 ¶ 112. In March 2012, the FDA issued Draft Guidance in which it outlined its “current thinking on the potential human health risks associated with exposure to . . . DBP.” D. 456-3 at 109. In December 2012, the FDA released Final Guidance on the subject. D. 450 ¶ 50; D. 510 ¶ 50. Like the Draft Guidance, the Final Guidance communicated the FDA's thinking on the health risks associated with exposure to DBP and clarified that it merely provided recommendations rather than directives. D. 456-11 at 178. The Division of Gastroenterology and Inborn Errors Products recommended that “it was prudent to change the professional labeling of Asacol [400mg] to provide information on the effects of DBP in animals and humans, as well as requiring the sponsor to reformulate their product without DBP.” D. 450 ¶ 67; D. 510 ¶ 67; D. 456-6 at 64. The FDA did not at any point pull Asacol HD from the market despite the fact that Asacol HD continued to have a DBP-containing coating until May 5, 2016. D. 509 ¶ 125; D. 545 ¶ 125.

         J. Generic Entry

         The parties dispute whether generic entry for Asacol 400mg would have occurred but for Warner Chilcott's decision to pull it from the market. The following facts relevant to that determination, however, are undisputed.

         First, Warner Chilcott was concerned about generic competition for Asacol 400mg. D. 509 ¶ 248; D. 515-10 at 2; D. 513-17 at 2; D. 509 ¶ 241; D. 545 ¶ 241; D. 514-39 at 6.

         Second, Warner Chilcott had an agreement with Lupin Pharmaceuticals, Inc. (“Lupin”), a generic manufacturer, to be an “authorized generic” - that is, Lupin would distribute Asacol 400mg supplied by Warner Chilcott as a generic product. D. 509 ¶ 266; D. 545 ¶ 266; D. 456-12 at 3. Under the terms of that agreement, Lupin was authorized to sell generic Asacol 400mg supplied by Warner Chilcott as soon as it was able, but only after another generic manufacturer had already entered the market for Asacol. D. 456-12 at 9. Lupin was to submit its first purchase order for generic Asacol 400mg from Warner Chilcott within 30 days of another manufacturer selling a generic version of Asacol 400mg. D. 456-12 at 10.

         Third, there is limited information regarding which, if any, generic manufacturers had filed ANDAs with a Paragraph III certification for Asacol 400mg. The FDA never filed any notice of either tentative or final approval of an ANDA for a generic version of Asacol 400mg. D. 450 ¶ 211; D. 510 ¶ 211. The parties agree that neither Lupin nor another manufacturer, Zydus Pharmaceutical (USA) Inc. (“Zydus”), filed an ANDA for Asacol. Lupin believed that nine manufacturers had filed Drug Master Files (“DMFs”), a filing regarding manufacturing processes for a product that might be used to support an ANDA filing. D. 509 ¶¶ 274-275; D. 545 ¶¶ 274-275; D. 515-14 at 3. There is no evidence about whether any of the following generic manufacturers had filed ANDAs with a Paragraph III certification for Asacol 400mg: Actavis Pharma. (“Actavis”), Mylan Pharmaceuticals, Inc. (“Mylan”), Teva Pharmaceutical Industries Ltd. (“Teva”), Watson Pharmaceuticals (“Watson”); Pendopharm, Sanis Health, Aspen Pharmacare, Dr. Falk GmBH, Merckle GmBH, Tillotts Pharma, Sandoz (Novartis), Aurobindo Pharmaceuticals, Torrent Laboratory Inc., West Coast, Zota Healthcare Ltd., Ipca Laboratories, Bracco, Chiesi, Crinos, Dorm, SOFAR, Wellpharma. D. 450 ¶¶ 206, 267; D. 510 ¶¶ 206, 267. Roxane Laboratories, Inc. (“Roxane”) and Par Pharmaceutical, Inc. (“Par”) had filed ANDAs with a Paragraph IV certification - certifying that their products did not infringe the patents associated with Asacol 400mg - but neither manufacturer proved bioequivalence to the FDA and those ANDAs were withdrawn. D. 509 ¶¶ 304-314; D. 545 ¶¶ 304-314.

         Fourth, it is not clear how long the FDA would have taken to approve an ANDA for generic Asacol 400mg once any ANDA was submitted. According to the FDA, its “median review time from ANDA receipt to approval” was 27.85 months in 2010 and 29.52 months in 2011, but the time for individual drugs might be significantly above or below that median. D. 450 ¶¶ 212-215; D. 510 ¶¶ 212-215. The FDA could have expedited review of the first ANDA for generic Asacol 400mg, as FDA policy allows expedited review of “first generic products for which there are no blocking patents or exclusivities on the reference listed drug.” D. 509 ¶¶ 316-17; D. 545 ¶¶ 316-17 Fifth, generic manufacturers had significant economic incentives to produce a generic version of Asacol 400mg if Warner Chilcott did not pull Asacol 400mg from the market and there is a dispute regarding whether they had the technical capacity to do so. D. 509 ¶¶ 284-85, 295-297; D. 545 ¶¶ 284-85, 295-297; D. 426-5 at 20. Generic manufacturers had already produced internationally delayed-release mesalamine oral tablets with a Eudragit S coating, similar to the Asacol 400mg tablet. D. 509 ¶ 296; D. 545 ¶ 296. Additionally, the FDA's decision to focus on PK testing rather than on clinical studies was considered by the Defendants to be “lowering the bar” to generic entry. D. 509 ¶ 289; D. 545 ¶ 289. The FDA had already approved two other oral mesalamine products based on bioequivalence, and, on July 21, 2017, approved a generic version of Asacol HD. D. 509 ¶¶ 318-19; D. 545 ¶¶ 318-19.

         After Delzicol launched, Mylan, Teva and Zydus filed ANDAs for Delzicol with Paragraph IV certifications. D. 450 ¶ 328; D. 510 ¶ 328.

         K. Other Ulcerative Colitis Treatments

         There is a dispute between the parties regarding the extent to which Asacol 400mg is a product competing with other ulcerative colitis treatments. Before discussing the various facts relevant to that determination, however, it is useful to provide a brief overview of the way pharmaceutical products are purchased.

         Typically, a prescription drug is prescribed by a physician to a patient, who then takes that prescription to a pharmacy to fill. D. 453-1 at 18. The pharmacy typically orders the drug wholesale from the manufacturer and resells the drug to patients. Id. When a patient purchases a drug, if the patient has insurance, the patient will generally pay a portion of the cost of the drug, called a co-pay, and the insurer will pay the remainder. Id. Some health insurers contract with a pharmacy benefit manager (“PBM”) to manage the business of providing coverage for pharmaceutical products. Id. The PBM will determine the list of drugs that it will cover, known as the formulary, and determine what steps a patient must go through to receive coverage for a drug. Id. at 19. Some PBMs will establish a higher co-pay for some drugs than others; generic drugs typically have a lower co-pay than brand-name drugs. Id. Some PBMs rely on a “tiered” system, wherein the PBM requires the patient to try one drug, usually a cheaper drug, before providing coverage for another, usually more expensive drug. Id. Drug manufacturers set prices by determining the wholesale price it will charge to pharmacies, providing rebates to PBMs, and providing rebates to patients. Id. at 18.

         Asacol 400mg, Asacol HD and Delzicol were not the only drugs throughout this period that were approved as ulcerative colitis treatments. D. 450 ¶ 268; D. 510 ¶ 268. Other drugs approved by the FDA for the treatment of oral ulcerative colitis were, like Asacol 400mg, Asacol HD, and Delzicol, mesalamine-containing drugs: Apriso, generic mesalamine (including a generic version of Asacol HD authorized by Warner Chilcott), Lialda, and Pentasa; others still are treatments based on compounds that are, like mesalamine, a type of 5-aminosalicylic acid or 5-ASA: Colazal, generic balsalazide disodium, Giazo, Azulfidine, generic sulfasalazine, Azulfidine EN-tabs and generic sulfasalazine SR. D. 450 ¶ 268; D. 510 ¶ 268; D. 452 at 24. Between 2009 and 2017, the percentage of oral dosage 5-ASA drugs sold that were Asacol-branded products (Asacol 400mg, Asacol HD, or Delzicol) fell from 42.9% to 8.4%, and, by some measures, the total output fell as well. D. 450 ¶ 269; D. 510 ¶ 269; D. 509 ¶ 332; D. 545 ¶ 332. At the same time, the percentage of oral dosage 5-ASA drugs sold that were Lialda-branded products increased from 12.1% to 28.3% D. 450 ¶ 270; D. 510 ¶ 270.

         Some PBMs excluded Asacol products from their formularies while including other oral 5-ASA drugs or gave other 5-ASA drugs preferential treatment on their formularies with respect to tiers. D. 450 ¶¶ 294-301, 306, 310; D. 510 ¶¶ 294-301, 306, 310. In some cases, the PBMs explicitly drew comparisons between the pricing and effectiveness of various 5-ASA drugs in determining what drugs would be on formulary or how they would place in the tiers. Id Certain medical literature and certain gastroenterologists identified the various oral 5-ASA drugs as “therapeutically interchangeable.” D. 450 ¶¶ 313-14; D. 510 ¶¶ 313-14.

         Warner Chilcott continued to earn profits on the sale of Asacol-branded products. From 2009 to 2012, Warner Chilcott's gross margins on Asacol 400mg and Asacol HD ranged from 87% to 95%, and from 2013 to 2016, Warner Chilcott's gross margins for Asacol HD were 88% to 91% and for Delzicol were 86% to 90%. D. 509 ¶¶ 334-35; D. 545 ¶¶ 334-35.

         L. Plaintiffs

         The named Plaintiffs in this action are the Teamsters Union 25 Health Services & Insurance Plan (“Teamsters”), the NECA-IBEW Welfare Trust Fund (“NECA-IBEW”), the Wisconsin Masons' Health Care Fund (“Masons”), and the Minnesota Laborers Health and Welfare Fund (“Laborers”). The Teamsters are headquartered in Massachusetts, and the Plaintiffs contend that the Teamsters made purchases of Asacol 400mg, Asacol HD, or Delzicol in Massachusetts, New Jersey, Missouri, and New Hampshire during the relevant time period. D. 124 ¶¶ 13-14; D. 450 ¶¶ 335-336; D. 510 ¶¶ 335-336. The NECA-IBEW are headquartered in Illinois and made purchases of Asacol 400mg, Asacol HD, or Delzicol during the relevant time period in Indiana, Missouri, Wisconsin, Alabama, Florida, Illinois, Kentucky, and Kansas. D. 124 ¶ 15; D. 450 ¶ 337; D. 510 ¶ 337. The Masons are headquartered in Wisconsin and made purchases of Asacol 400mg, Asacol HD, or Delzicol in Wisconsin during the relevant time period. D. 450 ¶ 339; D. 510 ¶ 339. The Laborers are headquartered in Minnesota and made purchases of Asacol, Asacol HD, or Delzicol in Minnesota, Ohio, Wisconsin, Iowa, and Arizona during the relevant time period. D. 450 ¶ 340; D. 510 ¶ 340.

         III. Procedural History

         The procedural history of this case is recounted in detail in the Court's Memorandum and Order on the motion to dismiss, D. 110. Currently pending before this Court are the parties' motions to exclude expert testimony, D. 426; D. 427; D. 428; D. 429; D. 430; D. 431; D. 444, the Plaintiffs' motion for class certification under Fed.R.Civ.P. 23(b)(3), D. 380, and the Defendants' motion for summary judgment, D. 445. The Court held a hearing regarding these pending motions on October 26, 2017. D. 556.

         IV. Motions to Strike Expert Testimony

         A. Standard of Review

         Pursuant to Fed.R.Evid. 702, a qualified expert witness can testify “in the form of an opinion, or otherwise, if (1) the testimony is based upon sufficient facts or data, (2) the testimony is the product of reliable principles and methods, and (3) the witness has applied the principles and methods reliably to the facts of the case.” United States v. Mooney, 315 F.3d 54, 62 (1st Cir. 2002) (quoting Fed.R.Evid. 702). The district court is tasked with “ensuring that an expert's testimony both rests on a reliable foundation and is relevant to the task at hand.” Daubert v. Merrell Dow Pharm., Inc, 509 U.S. 579, 597 (1993). “[T]he district court must perform [this] gatekeeping function by preliminarily assessing ‘whether the reasoning or methodology . . . properly can be applied to the facts in issue'” by examining multiple factors through a case-specific inquiry. Seahorse Marine Supplies, Inc. v. P.R. Sun Oil Co., 295 F.3d 68, 80-81 (1st Cir. 2002) (quoting Daubert, 509 U.S. at 592-93). “As long as an expert's scientific testimony rests upon good grounds, based on what is known, it should be tested by the adversary process-competing expert testimony and active cross-examination-rather than excluded from jurors' scrutiny for fear that they will not grasp its complexities or satisfactorily weigh its inadequacies.” Ruiz-Troche v. Pepsi Cola of P.R Bottling Co., 161 F.3d 77, 85 (1st Cir. 1998) (citations omitted). “Vigorous cross-examination, presentation of contrary evidence, and careful instruction on the burden of proof are the traditional and appropriate means of attacking shaky but admissible evidence.” Daubert, 509 U.S. at 596.

         B. Motion to Exclude Testimony of Todd Clark

         The Defendants move to exclude the testimony of Todd Clark (“Clark”), an expert in the pharmaceutical industry, D. 426-5 at 3-4. Clark opines that “one or more generic versions of Asacol 400mg would have entered the market at or within a short time period after the product's July 2013 patent expiration if Warner Chilcott had not executed the Asacol-to-Delzicol hard switch.” D. 426-5 at 9.

         The Defendants first contend that Clark's opinion is speculative because it is impermissibly based on general industry information rather than actual data about which companies filed ANDAs in preparation for launch of a generic version of Asacol 400mg. D. 426-1 at 7-8. Specifically, the Defendants contend that information concerning whether generic manufacturers were technologically capable of producing a generic version of Asacol 400mg is “irrelevant” to the question of whether a generic manufacturer would have entered. D. 426-1 at 7.

         In forming his opinion, Clark relied upon “industry norms, [his] experience, the nature of the product, the number of companies that we do know were interested, [and] the number of companies that would typically be interested in a product of this size, ” in a “holistic approach” rather than a quantitative simulation. D. 426-3 at 21. In drafting the report, Clark reviewed historical data regarding generic entry, D. 426-5 at 16, both generally and specifically with respect to treatments for ulcerative colitis, D. 426-5 at 17; developments in the international market for mesalamine products, D. 426-5 at 21-22; the technical capacities of generic manufacturers to produce the drug, D. 426-5 at 35; the incentives for generic manufacturers to consider entering the market, D. 426-5 at 20; the ability of generic manufacturers to obtain FDA approval, based on guidance released by the FDA on the standards for bioequivalence, D. 426-5 at 42; ...


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