In Re Zantac (Ranitidine) Litigation

• Court: Superior Court of Delaware
• Decided: May 31, 2024
• Docket: N22C-09-101 ZAN
• Status: Published

Opinion

IN THE SUPERIOR COURT OF THE STATE OF DELAWARE

) IN RE ZANTAC (RANITIDINE) ) LITIGATION ) ) ) C.A. NO. N22C-09-101 ZAN ) )

Submitted: March 7, 2024 Decided: May 31, 2024 Corrected: June 3, 2024

OMNIBUS ORDER ON MOTIONS TO EXCLUDE EXPERT OPINIONS

I. INTRODUCTION

Nearly 75,000 Plaintiffs seek to be heard in Delaware for claims alleging that

their cancer was caused due to the ingestion of a heartburn medication commonly

known as Zantac. In this early stage of these proceedings, before the Court for

disposition are the parties’ competing motions to exclude expert testimony pursuant

to Rule 702 of the Delaware Rules of Evidence and Daubert v. Merrell Dow Pharm.

Inc.,1 (the “Motions”).

The Motions were the subject of discovery, a three-day “Daubert” hearing,

multiple layers of briefing, and post-hearing submissions all supported by more than

1 509 U.S. 579 (1993).

1 forty volumes of exhibits. Having considered the pleadings, oral arguments,

supplemental submissions, and the full record herein, for the reasons now stated, the

parties’ Motions are DENIED.

II. FACTUAL AND PROCEDURAL HISTORY2

This case involves a molecule known as ranitidine. Ranitidine is marketed

under the label name of Zantac. N-Nitrosodimethylamine (“NDMA”) is found in

ranitidine.3 NDMA causes cancer.4

Zantac is a part of a class of medications known as Histamine-2 Receptor

Antagonists (“H2Ras”).5 Ranitidine is a histamine-2 receptor blocker used to “treat

heartburn and many other gastro-intestinal disorders, including duodenal ulcers,

gastroesophageal reflux disease (“GERD”) and esophagitis.”6

In 1983, based on extensive testing, including humans, the FDA approved

ranitidine for prescription use to treat ulcers and later approved it to treat other

2 The recitation of the history and facts in this section are for context only. 3 See Plaintiffs’ Opposition to Defendants’ Motion to Exclude General Causation Experts’ Opinions at 14, Trans. ID 71670509 (Dec. 20, 2023) (herein “Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op.”). 4 Id. 5 Defendants’ Brief in Support of Brand Defendants’ and Patheon’s Motion to Exclude Plaintiffs’ General Causation Experts’ Opinions at 3, Trans. ID 71408977 (Nov. 15, 2023) (herein “Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op.”). 6 In re Zantac, 644 F. Supp.3d 1075, 1095 (S.D. Fla. 2022).

2 stomach and esophageal conditions.7 In 1995, the FDA authorized ranitidine for over-

the-counter (“OTC”) use.8 By 2004, the FDA had further approved higher dosages of

ranitidine for OTC use.9

Zantac was on the market for more than 35 years.10 During approximately four

decades of marketing, there were four brand pharmaceutical companies and generic

manufacturers that sold versions of the product.11 GlaxoSmithKline (“GSK”)

developed the medication and initially marketed it in prescription form. 12 In 1995,

GSK marketed it as an OTC in a joint venture with a predecessor of Pfizer.13 In 1998,

GSK transferred its rights to sell OTC Zantac in the U.S. to that Pfizer predecessor.14

In 2006, Defendant Boehringer Ingelheim (“BI”) acquired the rights to sell OTC

Zantac.15 In 2017, Defendant Sanofi began selling OTC Zantac after acquiring the

brand from BI.16

7 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 4. 8 Id. 9 Id. 10 Id. 11 Id. 12 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 4, n1. 13 Id. 14 Id. 15 Id. 16 Id.

3 In September of 2019, Valisure, an online pharmacy submitted a citizen petition

to the FDA claiming detection of “extremely high levels of N-Nitrosodimethylamine

(NDMA)” in ranitidine.17 Valisure reported NDMA at levels in excess of three million

nanograms per tablet. This far exceeded the limit of 96 nanograms per day that the

FDA had set for NDMA ingestion in the context of an unrelated class of medications.18

After reviewing Valisure’s petition, the FDA raised concerns about the testing

methodology.19 FDA and ranitidine manufacturers studied NDMA in ranitidine and

examined whether ranitidine use increases cancer risks in patients.20 Over the next

month, some tests revealed amounts lower than what Valisure reported, and some lots

tested revealed amounts below the acceptable daily intake (ADI).21

In September and October of 2019, then-existing ranitidine manufacturers

recalled their products. And by April 2020—after further testing confirmed NDMA

levels in some samples continued to exceed ADI—the FDA requested manufacturers

initiate a market withdrawal of all remaining batches then remaining on the market.22

After the recall of ranitidine-containing Zantac, litigation ensued around the country.

17 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 5. 18 Id. 19 Id. 20 Id. 21 Id. (citing FDA, FDA Statement: Statement on new Testing Results, Including Low Levels of Impurities in Ranitidine Drugs (2019) (Brown Decl. Ex. 89) at 1). 22 Id. at 8. 4 A. NATIONAL PROCEDURAL HISTORY - THE “MDL”23

To address these claims, on February 6, 2020, the United States Judicial Panel

on Multidistrict Litigation established a multidistrict litigation process (the “MDL”)

in the U.S. District Court for the Southern District of Florida in West Palm Beach for

all pretrial purposes. The Panel ordered federal lawsuits for personal injury and

economic damages from the purchase or use of Zantac to be transferred to the MDL.

As part of MDL management, a Census Registry (“The Registry”) was created

to allow the parties and the Court to “understand the nature of the unfiled claims that

are a part” of the MDL.24 The MDL Court held a Daubert hearing in early 2022.

On December 6, 2022, the MDL Court issued its opinion on Daubert and

summary judgment motions (“MDL Order”).25 In its 200-page opinion, the MDL

Court, in pertinent part, excluded those plaintiffs’ experts’ general causation opinions

and granted summary judgment for Defendants.26

B. LITIGATION IN OTHER STATES

Similar suits were also proceeding in state courts throughout the United States.

The largest one, other than here, was a coordinated proceeding in California, the

23 See generally, In re Zantac, 644 F.Supp.3d at 1095. 24 Id. at 1096. 25 As of the date of this ruling, it appears that the MDL decision is on appeal in the Eleventh Circuit Court of Appeals. 26 See generally, id. 5 Judicial Council Coordinated Proceeding (“JCCP”). In the California state court,

several thousand cases were being coordinated in the JCCP, with sixteen bellwether

trials scheduled for 2024. The JCCP Plaintiffs were pursuing their claims for the same

cancers claimed here. Those cases advanced beyond the general causation phase.27

C. THE PARTIES AND PROCEDURAL HISTORY HERE

Plaintiffs in this litigation were not before the federal MDL Court. Nor are the

experts the same. Plaintiffs here are pursuing ten cancers—bladder, esophageal,

gastric, liver, pancreatic, breast, colorectal, kidney, lung and prostate. Notably, in the

MDL, Plaintiffs’ Leadership (also not present here) notified that Court that it had

decided not to pursue general causation expert reports for breast and kidney cancers

and initially narrowed their list from ten to eight cancers.28 In January of 2022, they

again notified the MDL Court that they were not moving forward with certain cancers,

and again, narrowed the list to five cancers. Thus, five of the cancer claims here were

not before the MDL Court.29

In September of 2022, nearly 75,000 complaints were filed in this Court.

27 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex 75. 28 In re Zantac, 644 F.Supp.3d at 1098. 29 Id. (The MDL noted in its final disclosure that the plaintiffs in the MDL intended to “prove that ranitidine causes bladder, esophageal, gastric, liver, and pancreatic cancers (the ‘Designated Cancers’), as opposed to other cancers (‘Non-Designated Cancers.’). The Defendants do not address Non-Designated Cancers in the Daubert motions, so individual cases in which Plaintiffs allege their ranitidine use caused their Non-Designated Cancers remain pending at this time and are not the subject of this Order.”).

6 Plaintiffs allege Defendants collectively bear responsibility for their cancer

diagnoses, and the related injuries or deaths caused from their ingestion of the

medication known as Zantac.

The Defendants are GlaxoSmithKline LLC (“GSK”), Boehringer Ingelheim

Pharmaceuticals, Inc., Boehringer Ingelheim Corporation, and Ingelheim U.S.A.

Corporation (collectively, B.I.), Sanofi US Services Inc., Sanofi-Aventis U.S. LLC,

and Chattem, Inc. (collectively, “Sanofi), Pfizer Inc. (“Pfizer”) (together with all

those just mentioned are referred to as the “Brand Defendants”) and Patheon, (all

collectively “Defendants”).30

In these initial proceedings, the first phase addresses “general causation,”

which involves the question of whether the ingestion of this product is capable of

causing cancer as alleged. To carry their burden at this stage, Plaintiffs have retained

ten experts to offer opinions on general causation for the ten mentioned cancers.

Defendants move to exclude them all.31 Plaintiffs also move to exclude certain

opinions proffered by Defendants’ sole General Causation Expert, William C.

30 Brand Defendants’ and Patheon’s Motion to Exclude Plaintiffs’ Expert Dr. Charles Jameson, Trans. ID 71409144 (Nov. 15, 2023) (herein “Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Expert Dr. Jameson”). 31 Defendants move to exclude all of Plaintiffs’ General Causation Experts: Drs. Charles William Jameson, PhD; William Sawyer, PhD; Alfred I. Neugut, M.D., PhD; Vinod K. Rustgi M.D., MBA; Ioannis Hatzaras, M.D. MPH, PhD, F.A.C.S.; Dan J. Raz, M.D.; Bruce J. Trock, MPH, PhD; George Miller, M.D.; Pablo Leone, M.D.; and Vitaly Margulis, M.D. (collectively “Plaintiffs’ General Causation Experts”).

7 Zamboni, Pharm.D., PhD.

III. APPLICABLE LEGAL STANDARDS

As in any products liability case, each party bears the burden of proof on the

admissibility of their expert opinion testimony.32 Delaware Rule of Evidence 702

addresses the admissibility of expert testimony. It provides:

A witness who is qualified as an expert by knowledge, skill, experience, training, or education may testify in the form of an opinion or otherwise if:

(a) the expert’s scientific, technical, or other specialized knowledge will help the trier of fact to understand the evidence or to determine a fact in issue;

(b) the testimony is based on sufficient facts or data;

(c) the testimony is the product of reliable principles and methods; and

(d) the expert has reliably applied the principles and methods to the facts of the case.33 This rule is nearly identical to Federal Rule of Evidence 702.34 Our Supreme

Court has interpreted Federal Rule of Evidence 702, addressed the admissibility of

expert testimony,35 and adopted the holdings of Daubert v. Merrell Dow Pharm.,

32 Minner v. Amer. Mort. & Guar. Co., 791 A.2d 826, 843 (Del. Super. 2000). 33 D.R.E. 702. 34 Barrera v. Monsanto Co., 2019 WL 2331090, at *3 (Del. Super. May 31, 2019).; see also Minner, 791 A.2d at 833 n.2. 35 See Tumlinson v. Advanced Micro Devices, Inc., 81 A.3d 1264, 1269 (Del. 2013) (herein “Tumlinson”).

8 Inc. (“Daubert”) and its progeny as the correct interpretation of Delaware Rule of

Evidence 702.36

A. THE DAUBERT STANDARD

Decided in 1993 by the United States Supreme Court, Daubert is a name

well-known to most lawyers. Even so, the Court has urged litigants to appreciate

“the perspective from which this Court will view so-called Daubert motions, and the

process by which such motions will be addressed.”37 This encouragement merits

respect, as Daubert at first blush may seem contradictory, expanding the power of

the trial court by rejecting the “general acceptance” requirement for admissibility

while at the same time emphasizing the limitations on the court’s role in deference

to the role of the jury.38 And although Daubert rejected the exclusivity of the

“general acceptance” requirement, an expert’s “access to the courtroom is not

unfettered.”39

A few factors can be implicated in Daubert reviews. Some are enumerated in

Rule 702; others, some identified in Daubert, are deemed nonexclusive.40 But even

the expanded list is not exclusive. None of the Daubert factors, specific or

36 See M.G. Bancorporation, Inc. v. LeBeau, 737 A.2d 513, 522 (Del. 1999). 37 In re Asbestos Litig., 911 A.2d 1176, 1197 (Del. Super. 2006). 38 Minner, 791 A.2d at 841. 39 In re Asbestos Litig., 911 A.2d at 1197. 40 Daubert, 509 U.S. at 590. 9 otherwise, is binding on the trial court.41 The trial court also has broad discretion to

consider factors not articulated by Daubert.42

B. THE GATEKEEPER AND THE JURY

Predominant among Daubert’s holdings is the recognition of the trial court’s

role as gatekeeper. In that role, the “Trial Judge…insure[s] that the scientific

testimony is not only relevant but reliable.”43 While Daubert may require trial courts

to dive deeper into certain preliminary facts than had historically been the case, it

was not intended to abrogate the jury’s constitutionally protected role as the ultimate

fact-finder; a role the courts of this State defend vigorously.44 Daubert and its

progeny have repeatedly emphasized the importance of the trial system and the role

of juries as the ultimate arbiters in expert evidentiary issues.

Therefore, “[a]s a threshold matter, Daubert neither requires nor empowers

Trial Courts to determine which of . . . competing scientific theories has the best

performance.”45 Daubert “requires only that the trial court determine whether the

41 Tumlinson, 81 A.3d at 1269. 42 Id. at 1272–73; Long v. Weider Nutrition Group, 2004 WL 1543226, at *5 (Del. Super. June 25, 2004) (citing Kumho Tire Co., Ltd. v. Carmichael, 526 U.S. 137, 150 (1999)). 43 Minner, 791 A.2d at 843 (citations omitted). 44 In re Asbestos Litig., 911 A.2d at 1199; see. e.g., Kaur v. Bos. Sci. Corp., 2022 WL 1486178, at *3 (Del. Super. May 11, 2022) (an expert’s investigations and assumptions “are readily subject to cross examination and to evaluation by the fact finder . . .”). 45 Minner, 791 A.2d at 848 (citation omitted).

10 proponent of the evidence has demonstrated that scientific conclusions have been

generated using sound and reliable approaches.”46 But “the judge is not a scientist

and the courtroom is not a science laboratory.”47 Indeed,

“[i]t would be unreasonable to conclude that the subject of scientific testimony must be ‘known’ to a certainty . . . . [N]ot knowing the mechanism whereby a particular agent causes a particular effect is not always fatal to a plaintiff’s claim. Causation can be proved even where we do not know precisely how the damage occurred if there is sufficiently compelling proof that the agent must have caused the damage somehow.”48 As such, to determine the admissibility of scientific evidence consistent with

Daubert, the trial judge must determine whether:

(1) the witness is qualified as an expert by knowledge, skill, experience, training or education;

(2) the evidence is relevant;

(3) the expert’s opinion is based upon information reasonably relied upon by the experts in the particular field;

(4) the expert testimony will assist the trier of fact to understand the evidence or to determine a fact in

46 In re Asbestos, 911 A.2d at 1201; see also Minner, 791 A.2d at 842 (citations omitted). 47 Daubert, 509 U.S. at 596–97 (quoting “Introduction to Reference Manual on Scientific Evidence”, Fed. Jud. Ctr. at 2 (2000)). 48 Daubert v. Merrell Dow Pharms., Inc., 43 F.3d 1311, 1314 (9th Cir. 1995) (emphasis in original); accord, Bowen v. E.I. Du Pont de Nemours and Co., 2005 WL 1952859, at *9 (Del. Super. June 23, 2005) (herein “Bowen”), aff’d 906 A.2d 787 (Del. 2006) (explaining that the trial court need not “decide the admissibility of scientific evidence with the degree of certainty required in scientific circles”).

11 issue; and

(5) the expert will not create unfair prejudice or confuse or mislead the jury.49

The gatekeeper must apply these particular “factors in a flexible manner that

takes into account the particular specialty of the expert under review and the

particular facts of the underlying case.”50 “Where the question of admissibility is a

close one, exclusion of the evidence is not appropriate where cross examination, the

presentation of contrary evidence and careful instruction regarding the burden of

proof will insure that the jury is not misled or confused.”51 Restated, “[t]he reliability

requirement is not a tool for the Court to use to exclude questionably reliable

evidence.”52 This Court’s refusal to establish a bright line rule for proving causality

has previously been considered.53 And no doubt, “the requisite proof necessary to

establish causation will vary greatly case by case.”54

The Supreme Court in Daubert was more direct: “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

49 Bowen v. E.I. DuPont de Nemours & Co., Inc., 906 A2d 787, 795 (Del. 2006) (herein “Bowen I”). 50 Id.; Scaife v. Astrazeneca LP, 2009 WL 1610575, at *14 (Del. Super. June 9, 2009). 51 Bowen, 2005 WL 1952859, at *8, aff’d sub nom. Bowen II, 906 A.2d at 787. 52 Barrera, 2019 WL 2331090, at *10. 53 Id. at *5 (citing In re Zoloft, 858 F.3d 787, 783 (3d Cir. 2017)). 54 In re Zoloft, 858 F.3d at 787. 12 evidence.”55 Thus guided, courts confronted by “shaky but admissible evidence”

conduct their Daubert analyses “with a ‘liberal thrust’ favoring admission.”56

C. DAUBERT AND GENERAL CAUSATION CONSIDERATIONS

As the preliminary question concerns general causation, this Court finds the

federal district court’s approach in In re Roundup Products Liability Litigation57

instructive:

The question at this early phase in the proceedings - the ‘general causation phase - is whether a reasonable jury could conclude that glyphosate . . . can cause Non Hodgkins Lymphoma (“NHL”) . . . . There are two significant problems with the plaintiffs’ presentation, which combine to make this a very close question. * * * The evidence, viewed in its totality, seems too equivocal to support any firm conclusion that glyphosate causes NHL. This calls into question the credibility of some of the plaintiffs’ experts, who have confidently identified a causal link.

However, the question at this phase is not whether the plaintiffs’ experts are right. The question is whether they have offered opinions that would be admissible at a jury trial. And the case law - particularly Ninth Circuit case law - emphasizes that a trial judge should not exclude an expert opinion merely because he thinks it’s shaky, or

55 Daubert, 509 U.S. at 596. 56 Messick v. Novartis Pharmaceuticals Corp., 747 F.3d 1193, 1196 (9th Cir. 2014) (quoting Daubert, 509. U.S. at 588); M.G. Bancorporation, Inc., 737 A.2d at 522. 57 390 F.Supp.3d 1102 (N.D. CA 2018) (herein “In re Roundup”).

13 because he thinks the jury will have cause to question the expert’s credibility. So long as an opinion is premised on reliable science principles, it should not be excluded by the trial judge; instead, the weaknesses in an unpersuasive expert opinion can be exposed at trial, through cross- examination or testimony by opposing experts.58

In Kennedy v. Collagen Corp., the Ninth Circuit emphasized that, while

competing experts, science, experiments, and publications “may increase or lessen

the value of the expert’s testimony . . . their presence should not preclude the

admission of the expert’s testimony—they go to the weight, not the admissibility.”59

Also important in Daubert proceedings is the gravity of the decision to be

made. This Court in In re Asbestos Litig. placed particular emphasis on the risks

attending expert opinion decisions:

In the products liability context, an incorrect decision can either deprive a plaintiff of warranted compensation while discouraging other similarly situated individuals from trying to obtain compensation, or it can improperly impose liability in a manner that will cause the abandonment of an important product or technology. Either result is unacceptable. The Court must tread carefully.60

Notably, in Long v. Weider Nutrition Group, Inc.,61 this Court likewise

counseled judicial restraint from a different, but equally compelling, perspective:

58 Id. at 1108–09; see also Kennedy v. Collagen Corp., 161 F.3d 1226, 1229–31 (9th Cir. 1998). 59 161 F.3d at 1230–31 (italics in original) (quoting McCullock v. H.B. Fuller Co., 61 F.3d 1038, 1044 (2d Cir. 1995). Accord, In re Asbestos Litig., 911 A.2d at 1180. 60 In re Asbestos Litig., 911 A.2d at 1200. 61 2004 WL 1543226, at *1. 14 The first of several victims of a new toxic tort should not be barred from having their day in court simply because the medical literature, which will eventually show the connection between the victims’ condition and the toxic substance, has not yet been completed.62

The cautions urged in In re Asbestos and Long seem self-evident even where

the plaintiffs are few. Here, where there are nearly 75,000 plaintiffs, the implications

are much more profound. Therefore, this Court proceeds cautiously.

IV. DISCUSSION

A. THE DISCRETIONARY MDL ORDER

Defendants extol the MDL Court’s decision with great fervor.63 Several issues

confound that reliance. First, the Delaware Supreme Court has made plain that

issues of admissibility, as procedural questions, are governed by Delaware law. 64

Therefore, Delaware evidentiary decisions control here.65

For example:

• that an expert may change her opinion goes to the weight, not the admissibility, of the expert opinion;66

• the use of animal studies in the course of an expert 62 Id. at 6 (quoting Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1208–09 (8th Cir. 2000)). 63 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 13–37. 64 Tumlinson, 81 A.3d at 1270. 65 Id. at 1273 (stating that it is improper to consider the law of a foreign forum when the admissibility of evidence is a Delaware issue). 66 Barrera, 2019 WL 2331090, at *11. 15 analysis does not bar admissibility of the expert opinion on human disease;67

• Delaware law holds that statistical significance is “not necessary to prove causality”;68

• Delaware does not recognize a “threshold dose” requirement as part of the general causation analysis; an issue discussed below;69

• epidemiological studies are not required as a threshold for the admission of an expert opinion on general causation.70

Second, the MDL Order concerned the exclusion of different experts; none of

whom are designated nor challenged here.71

Third, similar to other state courts that considered and opted not to be bound

by the MDL Order (e.g., the California JCCP Court) so, too, here, this Court views

the MDL Order as a “discretionary decision on the exclusion of evidence.”72 “Two

different trial judges can review the same evidence, weigh the evidence differently,

67 Id. at *14. 68 Id. at *4; see In re Zoloft, 858 F.3d at 793. 69 Barrera, 2019 WL 2331090, at *5. 70 Long, 2004 WL 1543226, at *6; see also Tumlinson v. Advanced Micro Devices, Inc., 2013 WL 7084888, at *9 (Del. Super. Oct. 15, 2013) (herein “Tumlinson II”), aff’d, 81 A.3d 1264 (Del. 2013) (stating that the Bradford Hill factors are not all-inclusive and only establish a framework to establish causation). 71 See Index of Exhibits in Support of Plaintiffs’ Opposition to Defendants’ Motion to Exclude Plaintiffs’ General Causation Experts’ Opinions, Trans. ID 71666233 (Dec. 20, 2023) (herein the exhibits will be cited in reference to the corresponding motion, such as “Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op., Ex. _”) Ex. 75 at 8. 72 Id. at 6. 16 and make different decisions . . . .”73 This is especially true where the evidentiary

law governing some of the salient issues differs. Defendants’ praise of the MDL

Court’s rationale breathes not a whisper to the differences in Delaware law

implicated here.

Fourth, as the preceding discussion reflects, Delaware courts approach

Daubert decisions cautiously and with deep deference for the role of juries as the

ultimate fact finders. To that end, our trial courts need not definitely “resolve” every

expert query posed, even those that might present “close calls” or “shaky opinions.”

When experts disagree, or credibility or other questions confound the reliability

issue, resolution of those issues rests with the jurors.74 Delaware courts are loath to

step into the heart of technical debate between opposing scientists. In that regard,

the jurisprudence reflected in the Floridian Zantac differs from Delaware’s. This

Court—with great respect for the hard judicial work done there—distinguishes that

ruling from what was presented here.75

73 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 34; Ex. 75, at 6. 74 In re Asbestos Litig., 911 A.2d at 1207. 75 The post-Daubert briefing here followed adjournment of the three-day Daubert hearing. Defendants’ submissions are noteworthy only for their zealous endorsement yet again of In Re Zantac and ask this Court to agree that “[the] MDL Decision is a Roadmap for this Court.” Of the 18 pages of argument in their Opening Post-Daubert brief, 14 pages are devoted to the MDL Order, which this Court has already addressed. Defendants also again cite to Long v. Weider Nutrition, 2004 WL 1543226 (Del. Super. June 25, 2004). See id., at 5. This Court affords great deference to the Long decision: in a case of this legal and medical gravity, the Court should proceed cautiously. See Long, 2004 WL 1543226, at *6; see also In re Asbestos, 911 A.2d at 1200. 17 B. GENERAL CAUSATION FOCUSES ON NDMA

The discrete issue before the Court at this stage is whether NDMA can cause

cancer. Both sides disagree as to how to frame the general causation question.

Plaintiffs cast the issue directly:

It is undisputed that N-Nitrosodimethylamine (“NDMA”) is found in ranitidine and that NDMA causes cancer. That is why the U.S. Food and Drug Administration ordered an immediate recall after independent testing showed unacceptable levels of NDMA in the drug. In turn, it would seem obvious then, that if a person ingested ranitidine with NDMA, they could develop cancer.76

Plaintiffs maintain that the issue is not whether ranitidine, untethered to

NDMA, can cause cancer because the cancer-causing agent is NDMA, and its route

of exposure to NDMA is through the ingestion of ranitidine.77

Conversely, Defendants frame the general causation question as turning on

“the consensus of the scientific community that ranitidine use does not increase the

risk of cancer, and the unreliable methodologies employed by Plaintiffs’ experts []

to avoid that reality.”78 In support, Defendants cite the “largest and highest quality

healthcare databases,” “leading medical journals,” “40 medical institutions, research

76 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 14 (emphasis in original). 77 Id. at 40 (emphasis in original). 78 Brand Defendants’ Opposition to Plaintiffs’ Motion to Exclude Certain Opinions of Defendants’ Expert William C. Zamboni at 1–2, Trans. ID 71683862 (Dec. 22, 2023) (herein “Brand Defs.’ Opp’n to Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Zamboni”) (emphasis added). 18 topics” and “15 peer-reviewed studies” addressing “whether ranitidine causes

cancer.”79 Defendants add that these “studies of ranitidine necessarily account for

any exposure to NDMA contained in ranitidine products.”80

Yet, Defendants do not dilate on how the studies “necessarily account” for

any exposure to NDMA contained in ranitidine products. Whether describing source

documents, like those above, or setting the predicate for a point of advocacy,

Defendants speak in terms of ranitidine: “patients who took ranitidine,”81 “whether

ranitidine causes cancer,”82 “studies of ranitidine,”83 “exposure to NDMA contained

in ranitidine,”84 “‘no demonstrable association’ between ranitidine use and any

cancer types[,] ranitidine patients,”85 and “real-world ranitidine data in humans.”86

At the same time, Defendants concede that in September and October of 2019,

“as a precautionary public health measure, then-existing ranitidine manufacturers

voluntarily recalled their ranitidine products pending further investigation into the

79 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 9–13 (emphasis added). 80 Id. at 10 (emphasis added). 81 Id. at 9. 82 Id. at 10. 83 Id. 84 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. 85 Id. 86 Id. at 11 (quotation marks in original); see also id. at 12 (“[N]o evidence of a causal association between ranitidine therapy and . . . cancer . . . none of these organizations has concluded that ranitidine use increases the risk of any type of cancer.”). 19 potential root-causes of NDMA found in some lots” of ranitidine.87 Defendants

likewise acknowledge that, in April 2020, after “further investigation” confirmed

that NDMA levels in some samples continued to exceed the ADI, the “FDA

requested that manufacturers initiate a market withdrawal of any batches remaining

in the market.”88 The recall was based on the FDA’s conclusion that NDMA is a

“substance that can cause cancer.”89

Since the FDA recall, ranitidine is no longer sold in the United States and

many other parts of the world.90 Plaintiffs emphasize that no evidence has been

offered that the FDA ever stated that ranitidine is safe to be returned to the market

or that any Defendant has sought to do so.91 And although Defendants place little

significance on the recall, they also do not challenge that assertion.

Instead, they rely on an FDA July 2021 study (Florian) to suggest that its

findings “do not support that ranitidine is converted to NDMA in a general, healthy

population.”92 This does little to advance their arguments. If that were the only

87 Id. at 8 (emphasis added). 88 Id. (emphasis added); In re Zantac, 644 F.Supp.3d at 1095–96. 89 Plaintiffs’ Brief in Support of Plaintiffs’ Motion to Exclude Certain Opinions of Defendants’ Expert Dr. William C. Zamboni, Trans. ID 71466806 (Nov. 21, 2023) (herein “Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni”) at 2. 90 In re Zantac, 644 F.Supp.3d at 1091–92; see also Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 4. 91 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 19. 92 Id. at 11 (emphasis added) (referring to the Florian study). 20 issue here, that study might have some utility.

Zantac was not marketed to serve a generally healthy population. It was

intended to treat persons with heartburn, and many other gastro-intestinal disorders,

including duodenal ulcers, gastroesophageal reflux disease (“GERD”) and

esophagitis. Notably, the record suggests that at least one defendant understood the

importance of marketing it to this population. The record suggests that Defendant

GSK’s marketing efforts, from day one, focused on the off-label promotion of

Zantac for long-term use, despite the drug’s approved indication only for short-term

use. One GSK executive expressed that very sentiment in 1983.93

Nevertheless, Defendants insist that the inquiry should focus on ranitidine, not

NDMA.94 That focus is understandable, but the Court cannot turn a blind eye to the

focus on NDMA, especially where the record suggests that Defendants

acknowledged the dangers of it:

On September 25, 2019, GSK’s scientists prepared a Hazard Assessment Report on NDMA (“Hazard Assessment”) to “protect the scientists and anybody handling” NDMA in the laboratory.95 Some of its

93 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 33, at 2 (“The sheer size of this opportunity and the potential rewards from it dwarf anything we’ve done so far. It’s not just that Zantac is bigger than all our other products put together . . . It’s bigger than the whole company. You’ve all heard the numbers. My mind finds it difficult to absorb all those zeroes . . .”). 94 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 9–10. 95 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 12, at 16:1–17 (emphasis added). 21 conclusions:

[NDMA] is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. * * *

There is overwhelming evidence that NDMA is mutagenic and clastogenic . . . Positive results have been observed in human as well as rodent cells.

* * *

Qualitatively, the metabolism of NDMA appears to be similar in humans and animals; as a result, it is considered highly likely that NDMA is carcinogenic to humans, potentially at relatively low levels of exposure.

* * * NDMA is a genotoxic carcinogen, and exposure should be reduced to the extent possible.

N-nitrosamines such as NDMA [] are considered carcinogens and have been implicated in human cancers such as bladder, esophagus, stomach and naso-pharynx.96

This fundamental dispute of whether the science should focus on ranitidine

versus NDMA lies at the heart of every challenge mounted in the Motions. This

Court was confronted with a similar issue in In re Asbestos Litig. The Court’s ruling

there speaks to Defendants’ ranitidine premise:

Plaintiffs must establish that their experts can reliably conclude that exposure to friction products increases the risk of contracting an asbestos-related disease. This does 96 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 19–20; Ex. 13, at 2. 22 not, however, preclude the plaintiffs from attempting to carry this burden by presenting competent evidence that friction products, in certain circumstances, release respirable products [that can cause cancer].97

Similarly, in Kennedy, the Ninth Circuit rejected the trial court’s refusal to

consider collagen in a general causation analysis, emphasizing that “the body breaks

down the collagen into amino acids, which are then absorbed into the body.”98 The

Kennedy court reversed the trial court’s ruling, finding that such evidence will assist

the trier of fact and is therefore admissible under Daubert and Rule 702.99 At this

stage, the particular facts here compel the same conclusion.

For these reasons, this Court cannot constrain its gatekeeping function solely

to the studies related to ranitidine. NDMA’s dangers, the science, the studies, and

the opinions therein must be given due consideration.

The Court now considers the specific challenges as to each expert.

C. PLAINTIFFS’ DAUBERT CHALLENGE

Defendants have disclosed William C. Zamboni as their sole causation expert.

Dr. Zamboni will opine, in part, that Defendant GSK’s Tanner study, discussed

below, is the type of study “often not submitted to FDA nor requested by the

97 In re Asbestos Litig., 911 A.2d at 1202 (emphasis added); see also Kennedy, 161 F.3d at 1229. 98 Kennedy, 161 F.3d at 1229 (emphasis added). 99 Id. at 1231; see also Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 75 at 33–34 (holding that cases in California “do not suggest that experts cannot consider studies on NDMA and must rely on epidemiology studies regarding ranitidine.”). 23 FDA.”100 Dr. Zamboni bases that conclusion on his “experience with drug

development.”101 Plaintiffs move to exclude that one sentence opinion as wholly

speculative, citing, inter alia, Dr. Zamboni’s lack of relevant experience in FDA

drug applications and his failure to review or consider documents relevant to the

FDA’s request of GSK for data on ranitidine studies.102 Plaintiffs do not move to

exclude the “majority” of Dr. Zamboni’s opinions.103

Instead, they urge that “an expert is not permitted to opine on the FDA’s state

of mind,” which, they claim, is exactly what Dr. Zamboni is doing. 104 Defendants

do not quarrel with that proposition.

The Court is constrained to pause on the context in which Plaintiffs’ Motion

arises. Plaintiffs dedicate considerable argument to what it characterizes as GSK’s

concealment of material science pertaining to NDMA beginning in 1982. Plaintiffs’

100 Brand Defs.’ Opp’n to Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 3 (citing Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni Ex. 2, at 28). 101 Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 28; Ex. 2 at 1–2. 102 Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 29 (“Dr. Zamboni’s opinion regarding what the FDA would not want to know was rendered without reference to the very document summarizing what [information] the FDA requested.”). 103 Id. at 2 n.1. 104 Plaintiffs’ Reply in Support of Plaintiffs’ Motion to Exclude Certain Opinions of Defendants’ Expert Dr. William C. Zamboni, Trans. ID 71806319 (Jan. 12, 2024) (herein “Pls.’ Reply in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni”) at 1. 24 effort is detailed and grounded in quotations from GSK and FDA documents.105

By way of background, Plaintiffs allege that as early as 1982, before Zantac

was approved by the FDA, GSK conducted tests that directly linked ranitidine to

NDMA formation. A 1982 series of tests, called the Tanner study, named for the

scientist who performed and reported on the tests, has become a focus of the parties

here.106 Plaintiffs assert that the Tanner study found that “molecules . . . like

ranitidine, can react with nitrite under certain conditions to yield [NDMA].”107

Therefore, NDMA “was already a well-established genotoxic and mutagenic

nitrosamine.”108

The Tanner Study was only “circulated internally at GSK.”109 Beginning in

1980, prior to FDA Approval of Zantac, the FDA had voiced concerns about the

nitrosation potential of ranitidine.110 It is alleged that GSK met with the FDA in

May 1982, to discuss ranitidine’s mutagenicity and nitrosation. Neither the Tanner

Study nor NDMA was raised by GSK.111 The meeting never reached those topics

105 See Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 4– 24. 106 Id. at 11. 107 Id. (internal quotes omitted). 108 Id. (emphasis omitted). 109 Id. 110 Id. at 5 (quotation omitted). 111 Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 12–13. 25 and the Tanner Study was not made public until 2019.112

In the intervening years, Zantac went through the FDA pre-approval process.

The FDA requested of GSK specific information relative to nitrosation and

ranitidine. Despite various interactions with the FDA, and additional internal testing

and reports, GSK did not disclose the Tanner Study until 2019.

Plaintiffs allege that for almost four decades GSK “concealed the fact that

ranitidine degrades into NDMA.”113 Defendants dispute Plaintiffs’ allegations,

emphasizing both that 1) substantively, that the Tanner Study addresses whether

ranitidine “reacts with nitrite within the human stomach to form NDMA”, that is,

endogenously;114 and 2) procedurally, that the Tanner study was a type of study

“often not submitted to FDA nor requested by the FDA.”115 Dr. Zamboni bases that

conclusion on his “experience with drug development.”116

The potential implications of the Tanner Study were compounded by a 1984

report—the Preliminary Results of an Investigation into the Thermal Degradation of

Ranitidine Hydrochloride (“Preliminary Results”)—where GSK reported that

112 Id. at 2, 23. 113 Brand Defs.’ Opp’n to Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Zamboni at 2; 2 n.5. 114 Id. 115 Id. at 1 (quoting Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni Ex. 2, at 28). 116 Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni Ex. 2, at 28. 26 ranitidine would rapidly degrade in the presence of moisture and heat, yielding

“unidentified, breakdown products . . . within the liquid mass formed as a result.”117

Plaintiffs allege that, despite the Tanner Study, the Preliminary Results report and

numerous other inquiries and opportunities to do so, GSK did not test the

unidentified breakdown products for NDMA.118 The Tanner Study remained

internal.

Furthermore, when ranitidine breaks down to NDMA, discoloration can

indicate that this degradation process has begun.119 It is alleged that after concluding

that discoloration could not be avoided, GSK scientists recommended changing the

color of the tablets to “mask any potential discoloration.”120 That recommendation

was accepted.121 Plaintiffs point to these issues to support the notion that GSK had

knowledge of the dangers associated with NDMA as early as 1982.122

Defendants devote the majority of their opposition contesting Plaintiffs’

history.123 The one sentence in Dr. Zamboni’s opinion which Plaintiffs move to

117 Id. at 19; Ex. 27, at 2. 118 Id. 119 Id. at 20–21 (responding to the discoloration problem, one GSK scientist asked, “surely [the discoloration] begs the question, ‘if it changes with time, is it safe to use?’ . . . which we do not have sufficient information on.”) (quoting Ex. 33 at 5); Ex. 28–31. 120 Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 20; Ex. 28, at 1; Ex. 29, at 1; Ex. 30, at 6. 121 Id. 122 Pls.’ Br. in Supp. of Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Dr. Zamboni at 2–3. 123 Brand Defs.’ Opp’n to Pls.’ Mot. to Exclude Certain Op. of Defs.’ Expert Zamboni at 6–15. 27 exclude seems intended to support Defendants’ challenge of GSK’s failure to

disclose the Tanner Report, and any other data, until 2019. The potential

implications of Plaintiffs’ history are disturbing. But it is not for the Court to plumb

their depths at this time.

It may be more than generous to call Dr. Zamboni’s opinion “shaky.”124 But,

as Daubert and progeny teach us, “[t]he reliability requirement is not a tool for the

Court to use to exclude questionably reliable evidence.”125 The one sentence opinion

of Dr. Tanner targeted by Plaintiffs’ Motion will not be excluded. Dr. Zamboni can

testify to that assertion, though his testimony on that issue should be limited to the

discrete issue which Plaintiffs move to exclude. Plaintiffs are not without recourse.

His opinion can be properly measured by cross examination.126 Plaintiffs’ Motion

to Exclude Certain Opinions of Defendants’ Expert William C. Zamboni is

DENIED.

D. DEFENDANTS’ BROAD DAUBERT CHALLENGES

Defendants muster several broad challenges to general causation. Most of

these are asserted in the context of Defendants’ Motion to exclude certain experts

124 In re Roundup, 390 F.Supp.3d at 1109. 125 Barrera, 2019 WL 2331090, at *10. 126 In re Roundup, 390 F.Supp.3d at 1109 (“[T]he weaknesses [in an] unpersuasive expert opinion can be exposed at trial, through cross-examination or testimony by opposing experts”); see also Kaur, 2022 WL 1486178, at *3 (“[C]hallenges to the ‘factual basis of an expert opinion go to the credibility of the testimony, not the admissibility, and it is for the opposing party to challenge . . . the expert opinion on cross-examination.’”). 28 and are addressed below.

One challenge merits discussion at the outset: Plaintiffs’ alleged failure to

offer satisfactory proof of threshold dose.127 Plaintiffs rely on In re TMI Litig.,128

where the Third Circuit Court recognized that “it is currently believed that there is

no threshold dose below which the probability of cancer induction is zero.”129

Defendants point to Tumlinson II130 in support.131

In Tumlinson II, this Court was confronted with a causation question

involving ten possible airborne, causative agents. Plaintiffs’ expert did not rely on

a dosage in her causative analysis “but instead on atmospheric concentration ranges

as a surrogate.”132 Tumlinson recognized that no black letter requirement for

threshold dose exists. To the contrary, the Court discussed those cases excusing

threshold dose, emphasizing that “[i]n each case, however, the substance in question

127 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 32; see Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 79–84; see also Reply Brief in Support of Brand Defendants’ and Patheon’s Motions to Exclude: (1) Plaintiffs’ General Causation Experts’ Opinions; and (2) Dr. Charles Jameson, Trans. ID 71797654 (Jan. 12, 2024) (herein “Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson”) at 32–35. 128 193 F.3d 613 (3d Cir. 1999), amended, 199 F.3d 158 (3rd Cir. 2000). 129 Id. at 642. In re TMI is not mentioned in Defendants’ Opening or Reply brief, and Defendants do not discuss threshold dose in their Reply. 130 Tumlinson II, 2013 WL 7084888, at *7. 131 See Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 32–36; Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson at 32–35. 132 Tumlinson II, 2013 WL 7084888, at *7. 29 is known to be harmful at some level and the plaintiff suffered the precise harm

connected to that exposure.”133

The first prong of Tumlinson II’s comment goes to general causation; the

second to specific causation.134 Ostensibly, Defendants’ focus on “precise harm” is

intended to require something more than cancer.135 The Court rejects such a precious

reading, at least at the general causation phase, especially given the conclusions of

GSK’s 2019 Hazard Assessment, quoted at length above. Daubert counsels against

black letter standards. Like general acceptance and statistical significance, threshold

dose is another factor to be considered in the Daubert analysis, but its presence or

absence is not outcome determinative.

Moreover, the record suggests that Defendants, particularly GSK, have been

on notice of the harm that can result from NDMA in their product since the Tanner

Study in 1982. The Hazard Assessment reflects GSK’s own conclusions about

carcinogenicity and NDMA.136 Defendants’ expert testified that threshold dose is a

133 Id. 134 See id. at *5, 8 (“General causation does not consider the likelihood that a certain exposure caused a certain harm. Rather, it only considers the possibility.”); see also Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 84 nn.271–273; Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson at 33. 135 See Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson at 33. 136 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 12, at 16:1–17. 30 “somewhat meaningless statement [] scientifically.”137 Defendants debate the

meaning of that concession.138 Resolution of that debate awaits the jury’s attention.

But Daubert supports broad, flexible consideration at this stage.

Also, the parties do not dispute that the FDA has established an ADI limit for

NDMA based on cancer risk.139 Plaintiffs maintain the testing evidence shows “that

ranitidine products expose consumers to levels in excess of that ADI.”140 The

Hazard Assessment provides strong evidence that GSK admits the carcinogenic

threat in NDMA.141

Notwithstanding Defendants’ vigorous quarrel with the implications drawn

from the Tanner history, it can fairly be inferred that GSK delayed revealing the

cancer-causing potential of NDMA into the science marketplace. Plaintiffs should

also be able to argue inferences that the collective delays by all Defendants

forestalled development of the science of NDMA exposure.142 At this stage, it does

137 Id. at 81; id. at 81 n.264. 138 Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson at 32. 139 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 83, 83 n.265; Ex. 84, at 8 (stating that the ADI “is a level that approximates an increased cancer risk”). 140 See id. at 83, 92. 141 Id. Ex. 11 (e.g., “There is overwhelming evidence that NDMA is mutagenic and clastogenic . . . Qualitatively, the metabolism of NDMA appears to be similar in humans and animals; as a result, it is considered highly likely that NDMA is carcinogenic to humans, potentially at relatively low levels of exposure.”). 142 See Long, 2004 WL 1543226, at *6 (“[V]ictims of a new toxic tort should not be barred from having their day in court simply because the medical literature, which will eventually show the connection between the victims’ condition and the toxic substance, has not yet been completed.”). 31 not lie in the mouths of Defendants to assert a defense based on lack of threshold

dose. That issue awaits a specific causation finding by the jury.

This is not a case where the imposition of a bright line rule is appropriate.

That is not to suggest that [threshold dose] is irrelevant.”143 It remains, like general

acceptance and statistical significance, one of the factors enumerated by Daubert

and its progeny to be considered in the general causation analysis. But it is not, and

should not, be deemed, alone, outcome determinative. That consideration belongs

to the jury.

The Court now considers the specific challenges against Plaintiffs’ experts.

E. DEFENDANTS’ SPECIFIC DAUBERT CHALLENGES

1. Dr. Charles Jameson

Dr. Jameson has been asked to provide expert testimony on ranitidine’s ability

to form NDMA endogenously and exogenously and to provide “background

information about the mechanism through which NDMA causes cancer.”144

Dr. Jameson is a chemist and toxicologist specializing in carcinogenesis. He

began his career as a senior chemist at the National Institute of Health (“NIH”)’s

National Cancer Institute. Later, Dr. Jameson was responsible for the National

Institute of Health’s Environmental Health Services division of Toxicology

143 In re Zoloft, 858 F.3d at 793. 144 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 90. 32 Research and Testing. For 18 years, he served as a director on the National

Toxicology Program’s Report on Carcinogens.145 He has authored or co-authored

over 80 peer-reviewed scientific publications.146 Dr. Jameson’s methodology, when

called upon to provide expert testimony, has been upheld by this Court,147 as well as

the California court overseeing the JCCP, where he provided expert testimony on

NDMA and ranitidine.148 In both cases, Dr. Jameson’s testimony was admitted.

Defendants do not challenge Dr. Jameson’s qualifications to consider and opine on

the questions before him. Dr. Jameson offers four opinions here:149

• ranitidine produces NDMA exogenously (outside the body);

• ranitidine produces NDMA endogenously (inside the body);

• NDMA “meets 5 characteristics of the generally accepted characteristics of a carcinogen; and,

145 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 19. 146 Id., see also id. at 88–90 (providing a complete summary of Dr. Jameson’s qualifications). 147 See Barrera, 2019 WL 2331090, at *14. 148 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 88; Ex. 75. 149 The scope of Dr. Jameson’s opinion is specifically defined. Yet defendants challenge his failure to opine “that NDMA in ranitidine can cause cancer in any of the ten cancers at issue,” a topic on which he is not offering an opinion. Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson at 5. Calling that the “central issue at this stage” of the case, defendants argue that Dr. Jameson’s expert testimony is “irrelevant.” Id. at 6. The Court rejects that conclusion. Endogenous and exogenous formation of NDMA are a part of plaintiffs’ case, as are the carcinogenic characteristics of NDMA and the generally accepted opinion among science researchers that NDMA is capable of causing cancer in animals, and humans; topics on which Dr. Jameson has been proffered, based on his review of scientific, chemical and medical data. 33 • “It is generally accepted among cancer science researchers that NDMA is capable of causing cancer in animals, including cancer in humans.”150

In support of his expert opinion, Dr. Jameson opines that “the level of NDMA

found in ranitidine upon its storage reaches levels that exceed the daily intake

limit.”151 In its root cause analysis, GSK likewise concludes that degradation of

ranitidine, which begins from the point of manufacture, increases NDMA levels, a

point confirmed by the FDA.152 This conclusion was also confirmed by independent,

peer-reviewed testing.153

In preparing his opinions, Dr. Jameson reviewed data about “exogenous

NDMA formation from ranitidine,” including testing by FDA, Australia’s TGA,

GSK, Sanofi, and Emery Pharma, among others.154 He considered GSK’s root cause

analysis which “concludes, definitively, that ranitidine decomposes into NDMA on

150 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 19, at 3; see id. at 90– 91. 151 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 19, at 11–12 (emphasis added). 152 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 15, at 9 (“NDMA levels in drug substances start to increase at a slow rate from the point of manufacture; both elevated temperatures and RH contribute to an increase in the rate of degradation”) (emphasis added); id. Ex. 19, at 7; id. Ex. 8, at 2 (“NDMA levels increase in ranitidine even under normal storage conditions…and may raise the level of NDMA in the ranitidine product above the acceptable daily intake limit”) (emphasis added); see also id. Ex. 19 at 7. 153 See id. Ex. 30, at 1. 154 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 91, 91 nn.292–93. 34 standing, exacerbated by heat and humidity.”155 Dr. Jameson holds a PhD in organic

chemistry, and opines as to the molecular reaction beneath the instability of the

ranitidine molecules.156 His opinion, which is confirmed by independent, peer-

reviewed testing, “strongly suggest[s] that environmental factors such as heat and

oxygen are involved in the formation of NDMA.”157

Dr. Jameson concludes that the “evidence is very strong that ranitidine

decomposes to NDMA which is formed because of an intermolecular degradation

reaction of the ranitidine molecules that occurs primarily in ranitidine formations”

and that the “level of NDMA formed in ranitidine upon its storage reaches levels

that exceed the daily intake limit.”158 This is the same conclusion reached in GSK’s

root cause analysis and by the FDA, as evidenced by Defendants’ recalling their

products from the market.159

Dr. Jameson reviewed in vitro and in vivo data, including numerous in vitro

studies prepared by Defendants and independent laboratories, and peer-reviewed

literature that, inter alia, support the formation of NDMA from ranitidine within the

155 Id. at 91–92, 92 n.294. 156 Id. at 92, 92 n.295. 157 Id., 92 n.296. 158 Id., 92 n.297. 159 Id. at 92–93, 92 nn.298–99. 35 human stomach when exposed to sodium nitrite.160 The in vitro data “demonstrates

that NDMA forms in conditions found in the human stomach.”161 Dr. Jameson also

relied on an Emery Pharma simulated food study designed to explore how ranitidine

interacted with nitrite to form NDMA.162 Using the food tests, Emery was able to

show that in simulated gastric fluid ranitidine reacts to form NDMA.163 In his

opinion and in his deposition, he explained his acceptance of or disagreement with

literature he reviewed or pressed upon him by Defendants’ counsel.164

Dr. Jameson also considered conclusions and recommendations from a litany

of federal and international agencies, as well as GSK’s internal studies, that NDMA

“should be regarded for practical purposes as if it were carcinogenic to humans.”165

Conclusions with which he agrees. Some of the agencies reaching that conclusion

include the FDA, the EPA, The Department of Health and Human Services’ Report

on Carcinogens, the U.S. Department Health and Human Services’ Agency for Toxic

160 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 19, at 7–9, 10–18; see id. at 93–94, 93–94 nn.300–311. 161 Id. 162 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 95, 95 nn.315–18. 163 See id. at 95–100. 164 See id. at 115–21. Beyond the ranitidine issue, Defendants challenge the science of the Hidajat study: the duration of the study, measurements of “actual NDMA” available, and estimates and imputations of NDMA detected and to which workers were exposed. These critiques go to weight and, as a consequence, fail to support the Motion. 165 See id. at 16–22 (quoting Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 1, at 36). 36 Substances and Disease Registry (“ATSDR”), and the World Health Organization

(“WHO”).166 It cannot be suggested that Dr. Jameson “neglected the core facts of

the case.”167 Upon completion of his review, he performed a Bradford Hill

analysis.168 Plaintiffs offer a brief comment on Bradford Hill analysis, none of which

is remarkable or cause for debate, but three points merit repetition:

(1) methods used by experts in forming opinions as to causation substantially rely on the expert’s judgment in selecting and weighing their sources;

(2) Daubert does not prescribe a specific weight that evidence should be given; and,

(3) it is not the Court’s role to weigh that evidence, second guess researchers or pass judgment on substantive issues.169

Dr. Jameson’s review supports his conclusion that ranitidine produces NDMA

endogenously and exogenously, meets five characteristics of the generally accepted

characteristics of a carcinogen, and is generally accepted among cancer science

researchers that NDMA is capable of causing cancer in animals, including cancer in

166 Id. at 16–19. 167 Kaur, 2022 WL 1486178, at *3. 168 Defendants do not voice challenges to Dr. Jameson’s Bradford Hill analysis, either in their Opening Brief (filed separately) in support of their Motion to Exclude certain of his opinions, or in their Reply Brief. Defendants include three pages on alleged failings they ascribe to Defendants’ Bradford Hill analyses, collectively, referring in that argument to “Plaintiffs’ experts” and “some” of them. This does not give fair notice of specific challenges to Plaintiffs, their experts, or the Court. Defendants in their arguments directed at specific experts do raise Bradford Hill, which arguments are addressed later in this ruling. 169 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 67–68. 37 humans.170

Defendants’ challenges to the reliability of Dr. Jameson’s methodology are as

follows: he cherry picked his evidence;171 did not rank or weigh his studies;172 the

tests do not imitate conditions in humans;173 his reliance on non-peer reviewed

studies;174 reliance on bad science and improperly rejecting or favoring unreliable

studies;175 and, generally, relying on unreliable exogenous studies.176 These

challenges are for the jury.

The Court finds he utilized sound scientific methodology in formulating his

opinions. His opinion is generally admissible.177 The science with which Dr.

Jameson approached his task here, detailed in Plaintiffs’ Opposition, commends that

170 Id. at 90–91. 171 Brief in Support of Brand Defendants’ and Patheon’s Motion to Exclude Plaintiffs’ Expert Dr. Charles Jameson, Trans. ID 71409144 (Nov. 15, 2023) (herein “Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Expert Dr. Jameson”) at 15. 172 Id. at 16; see Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 100, 100 n.321 (stating that regulatory and scientific bodies do not rank studies but simply assess their strengths and weaknesses); see also id. at 116–117 (responding to questions from counsel, Dr. Jameson explains his methodology and explains the strengths and weaknesses of pertinent studies). 173 Id. at 16; but see id. at 101, 101 nn.323–326 (rebutting the assertion that the tests do not imitate conditions in humans and relying in part on the Braunstein study). 174 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Expert Dr. Jameson at 16. 175 Id. at 17; but see Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 103– 20. 176 Id. at 18. 177 In re Asbestos Litig., 911 A.2d at 1204–06; In re Roundup, 390 F.Supp.3d at 1150–51 (admitting expert opinion where the expert “conducted a literature review and evaluated the quality of each of the studies”); See Barrera, 2019 WL 2331090, at *14, 17. 38 methodology.178 Defendants may reject that science and the conclusions Dr.

Jameson derives from it. But that makes for a battle of the experts; it does not make

Dr. Jameson’s opinion inadmissible.179 This dispute presents a classic battle of the

experts.180 Defendants’ Motion to exclude the expert opinions of Dr. Charles

Jameson is DENIED.

2. William Sawyer, PhD

Plaintiffs offer Dr. William Sawyer for one purpose: to “convert the inhalation

doses of NDMA observed in the Hidajat study into an equivalent oral dose.”181 Dr.

Sawyer was not proffered, and will not offer, an opinion on causation; similarly he

does not intend to discuss the “merits or demerits of any epidemiological study.”182

The express limits of Dr. Sawyer’s opinion notwithstanding, Defendants criticize

Sawyer for not opining on issues not within his specific task.183

178 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 103–120. 179 McCullock, 61 F.3d at 1044 (“Disputes as to the strength of [an expert’s] credentials, faults in his use of [a particular] methodology, or lack of textual authority for his opinion, go to the weight, not the admissibility of his testimony”) (parentheticals added); see also Karlo v. Pittsburgh Glass Works, LLC, 849 F.3d 61, 83 (3d Cir. 2017) (“The question of whether a study’s results were properly calculated or interpreted ordinarily goes to the weight of the evidence, not to its admissibility”) (citation omitted). 180 Long, 2004 WL 1543226, at *6. 181 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 121. 182 Id. at 122; Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Charles Jameson at 87, 89 (“Plaintiffs acknowledge Dr. Sawyer is not offering a general causation opinion”). 183 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 126–127; Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op.

39 Defendants’ challenges are several, but they focus on one primary issue: Dr.

Sawyer’s reliance on the 2019 Hidajat study. Defendants attack the Hidajat study

because, they say, it “did not involve ranitidine at all,”184 and stand on the limiting,

mechanistic distinction they draw on ranitidine’s role. But Dr. Hidajat did testify

that “[her] study provided important evidence of. . . the association between NDMA

exposure and cancer.”185 Thus, at this juncture, her study “fits” the facts of the case.

The science behind the Hidajat study, and Dr. Sawyer’s use of it, merits pause.

Beyond the ranitidine issue, Defendants challenge the science of the Hidajat

study:186 the duration of the study,187 measurements of “actual NDMA” available,188

and estimates and imputations of NDMA detected and to which workers were

exposed.189 These critiques go to weight and, as a consequence, fail to support the

Motion.190

The Hidajat study “followed 36,441 rubber workers for 49 years—the longest

& Dr. Charles Jameson at 89 (stating that Dr. Sawyer’s analysis “could not bridge the analytical gap” on cancer causation). 184 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 124, 126. 185 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 78–79. 186 Id. at 124–126. 187 Id. at 125. 188 Id. 189 Id. at 125–26. 190 Kaur, 2022 WL 1486178, at *4; Bowen, 2005 WL 1952859, at *8; McCullock, 61 F.3d at 1038. 40 follow-up (by 25 years) of any other study in this case.”191 The length of the follow-

up period allowed “near-complete dataset, with 94% of the cohort diseased.”192 To

estimate exposure to NDMA, the authors “developed a peer-reviewed matrix based

on the fumes at various locations in the rubber factories…[where workers were]

‘divided into quartiles of exposure,’ each quartile being compared to the first to see

whether greater NDMA exposure was associated with specific cancers.”193 The

Hidajat study documented a “clear dose-response relationship between NDMA

exposure and the development of bladder, esophageal, liver, lung, pancreatic,

prostate, and stomach cancer.”194 Because exposure in that study “was through

inhalation,” Dr. Sawyer “calculated what the equivalent lifetime oral dose would be

in each quartile.”195

Defendants protest that Dr. Sawyer’s method is “flawed because the amount

of bioavailable NDMA can depend on dose.”196 When challenged at his deposition,

he explained that “this was the appropriate method used by forensic

191 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 74, 74 nn.242–247. 192 Id. 193 Id. 194 Id. at 74–77 (noting Dr. Sawyer offers no opinions on these findings. His opinion is limited to “convert[ing] the inhalation doses of NDMA observed in the Hidajat study into an equivalent oral dose.” 195 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 74, 74 n.247. 196 Id. at 121–122; see Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 124–26. 41 toxicologists.”197 He further stated that “by using bioavailable data based on higher

doses, he actually made a more conservative estimate of how much NDMA exposure

is occurring in the Hidajat study.”198 That is, that he was erring “on the side of

caution,” as, Plaintiffs note, is “customarily done in toxicological dose

assessments.”199 This challenge, like the various challenges Defendants assert

against the Hidajat study, fails under Daubert and its progeny.

Dr. Sawyer’s opinion is limited, plainly so. He is not testifying on causation,

but instead on his conversion of inhalation dose to oral dose.200 Defendants reject

his science. Perhaps, as presented during oral arguments, his science may be a bridge

too far. But at this juncture, the criticisms go to weight and do not preclude

admission.201 Defendants’ Motion to exclude Dr. Sawyer is DENIED.

3. Alfred I. Neugut, M.D., PhD.

As his CV makes plain,202 Dr. Neugut is an accomplished epidemiologist at

Columbia University. Dr. Neugut received his MD and PhD from Columbia

197 Id. at 122, 122 n.409. 198 Id. 199 Id., 122 nn.409–411 (citing to deposition testimony); Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 136. 200 Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson at 89. 201 See Kaur, 2022 WL 1486178, at *4; see also Bowen, 2005 WL 1952859, at *8; see also McCullock, 61 F.3d at 1038. 202 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 54. 42 University and a fellowship in Medical Oncology at Sloan-Kettering Cancer Center

as well as Columbia. Dr. Neugut has published over 800 peer reviewed chapters and

papers and received over $60 million in funding from the National Cancer Institute,

American Cancer Society, Department of Defense, and various foundations. Dr.

Neugut has taught cancer epidemiology at Columbia for over 40 years.203

Here, he was tasked to “assess whether the ingestion of ranitidine,

contaminated with NDMA, is causally associated with the development of urinary

bladder cancer.”204 Dr. Neugut was disclosed by plaintiffs in the JCCP litigation to

offer general causation opinions on carcinogenicity and ranitidine.205 The JCCP

Court reviewed his methodology, found it to be reliable and denied defendants’

motion to exclude his opinions.206 The California Court of Appeals has also

acknowledged Dr. Neugut as “an expert in the areas of medical oncology and cancer

epidemiology.”207

His opinions were excluded in In re Roundup Products Liability Litig.,208 and

the Barrera Court—then relying on In re Roundup—also excluded his opinions.209

203 Id. 204 Id. at 5. 205 See id. Ex. 75, at 34–38. 206 See id. 207 Johnson, 266 Cal.Rptr.3d at 118, modified on denial of reh’g (Aug. 18, 2020). 208 390 F.3d at 1144–46. 209 Barrera, 2019 WL 2331090, at *15, 15 nn.199–200. 43 The Roundup court noted that Dr. Neugut was “eminently qualified and refreshingly

candid,” and lauded his reports as “high quality.”210 But that court was disturbed by

Dr. Neugut’s presentation, commenting on issues with his testimony, not reflected

in the written transcript.211 The Roundup Court quite correctly noted that “[e]ach

problem with Dr. Neugut’s testimony is not sufficient, on its own, to justify

exclusion.”212 The cases discussed cited herein confirm that point. As to statistical

significance, neither Delaware nor the Third Circuit requires “statistical significance

to prove causality.”213

In preparing his opinion on the question before him here, Dr. Neugut looked

at peer-reviewed literature on NDMA, ranitidine, and bladder cancer, and considered

the strengths and weaknesses of each study.214 He then prepared a forest plot

synthesizing the studies,215 which revealed a consistent increased risk of cancer.216

Dr. Neugut’s approach “reflects a sound methodology consistent with Daubert’s

210 In re Roundup, 390 F.Supp.3d at 1144. 211 Id. (The Roundup Court listed its reasons for its findings that Dr. Neugut’s opinion was not sufficiently reliable to be admissible. Two related to his conclusions: one to his characterization of glyphosate as something other than a hazard assessment, the other about an IARC conclusion as to the meaning of “a probable carcinogen,” and Dr. Neugut’s agreement in his deposition regarding associations between glyphosate and NHL). None of those issues present here. 212 Id. at 1146. 213 Barrera, 2019 WL 2331090, at *5, 5 n.56 (citing In re Zoloft, 858 F.3d at 793). 214 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 54, at 15–26; compare In re Roundup, 390 F.Supp.3d at 1144. 215 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 54, at 33. 216 Id.; see also id. at 126. 44 ‘reliability’ component.”217 Dr. Neugut’s review and synthesis of the data and his

creation of the forest plot make his opinion generally admissible.

Dr. Neugut then synthesized the literature using the Bradford Hill factors:

After reviewing the data and studies described above with regard to the association between ranitidine and bladder cancer and weighing the evidence in the light of the Bradford Hill criteria, it is my expert opinion, within a reasonable degree of medical certainty, that there is a causal association between ranitidine and urinary bladder cancer.

Again, there is good biological plausibility that supports this conclusion. Human epidemiologic studies address this finding, and many are large, well done, and present reasonable strong associations for the finding. Also, several studies of NDMA exposure support an association with bladder cancer.218

In response to Dr. Neugut’s review and opinion, Defendants pursue an

“unreliable methodology” analysis, which they begin with the suggestion that Dr.

Neugut applies a lower standard of proof in litigation than in his professional

work.219 Defendants do not make clear if they mean to say that Dr. Neugut’s opinion

217 In re Asbestos Litig., 911 A.2d at 1206. Accord, In re Roundup, 390 F.Supp.3d at 1150–51 (admitting expert opinion where the expert “conducted a literature review and evaluated the quality of each of the studies”). Compare id. at 1148 (excluding expert where the expert report “did not demonstrate that he engaged in his own objective analysis” of the medical literature on which he relied). 218 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 126. 219 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 105; Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 126–27. 45 is not made to a “reasonable degree of medical certainty.”220 If so, Dr. Neugut

declares directly that his opinion is provided to that degree of certainty.221

If Defendants’ challenge goes to Dr. Neugut’s call of the question, it is still

not a proper basis for excluding his opinions. “Disputes as to the strength of [an

expert’s] credentials, faults in his use of [a particular] methodology, or lack of textual

authority for his opinion, go to the weight, not the admissibility of his testimony.”222

That notwithstanding, Dr. Neugut applied the same “generally accepted scientific

and medical principles and methodologies” used by cancer epidemiologists.223 Any

challenge to his application of those methodologies goes to the jury.

Defendants also charge that Dr. Neugut’s analysis is “blatantly results-

oriented,”224 uses “cherry picked” data,225 “outcome driven reasoning,”226 and is

“flatly contradict[ed] by his prior [deposition] testimony.”227 These criticisms attack

the expert’s credibility, the bases and calculations underlying his opinion, or seek to

220 See Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 105. 221 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 127; see id. Ex. 54, at 35; Ex. 193, at 143:17–25, 144:2–19. 222 McCullock, 61 F.3d at 1044 (parentheticals added). 223 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 127. 224 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 110. 225 Id. at 109. 226 Id. 227 Id. at 107–08. 46 elevate Defendants’ science over that of Dr. Neugut.228 These are all arguments that

Daubert and its progeny reserve to the jury.229

As the gatekeeper, the Court has spent considerable effort in considering Dr.

Neugut’s opinion and Delaware’s jurisprudence on point. The Court is not bound

by the rulings made in RoundUp and Barrera excluding him, particularly given the

comments of the Court on the merits of his opinion, and the presentation of the

science presented here.

Every case is different. In this early phase of the litigation, the Court is more

compelled to its conclusion by the legal concepts that animate Daubert proceedings,

especially as they recognize and uphold the distinct roles of the Court as gatekeeper

and that of the jury as the ultimate fact finder, and by the encouragement of In re

Asbestos Litig. and Long to allow the jury to consider debatable scientific

approaches. Defendants can take up their challenges before the jury on cross

examination. Defendants’ Motion to exclude Dr. Neugut’s expert testimony is

228 Id. at 101–13. 229 See McCullock, 61 F.3d at 1038; see also Karlo, 849 F.3d at 83 (“The question of whether a study’s results were properly calculated or interpreted ordinarily goes to the weight of the evidence, not to its admissibility.”) (citation omitted); see also In re Roundup, 390 F.Supp.3d at 1150–51 (“different interpretations of [carcinogenicity] studies are not necessarily evidence of unreliability . . . plaintiffs may raise their concerns via cross-examination . . .”). 47 4. Dr. Vinod K. Rustgi

Plaintiffs ask Dr. Vinod Rustgi to provide “an expert opinion regarding the

role of high levels of NDMA found in ranitidine products in the risk of development

of Hepatocellular carcinoma” (“HCC”).230 Defendants do not challenge his

qualifications or his actual methodology of conducting a review of peer-reviewed

literature and applying the Bradford Hill factors.231

In conducting his analysis, Dr. Rustgi relied on in vitro data, in vivo data,

tissue culture and animal models, as well as epidemiological evidence in humans.232

Following a review of this data, and a Bradford Hill analysis, Dr. Rustgi concluded

that “NDMA-contaminated Ranitidine can cause the development of HCC.”233 This

base of analysis supports admissibility of Dr. Rustgi’s opinion.234

Yet Defendants challenge Dr. Rustgi’s opinion on several fronts. As

predicate, they argue that Dr. Rustgi concedes that “ranitidine or NDMA” is not

generally accepted by the community of liver specialists as a cause of liver cancer.235

230 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 138. 231 Id. 232 Id. 233 Id. (quoting Ex. 62, at 1). 234 In re Asbestos Litig., 911 A.2d at 1205–06; In re Roundup, 390 F.Supp.3d at 1150–51 (admitting expert opinion where the expert “conducted a literature review and evaluated the quality of each of the studies.”). 235 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 117. 48 But Daubert disposed of the general acceptance requirement for admissibility.236

Defendants urge that only one of seven epidemiological studies reported a

significant association between ranitidine and cancer. But Defendants note that

those “results have not been replicated in subsequent studies, and so could be due

to change.”237 Defendants cite the MDL Order from In re Zantac238 in support of

these arguments. For the reasons discussed above, this Court is not guided by that

ruling on these issues. Defendants’ qualification undermines the value of this point.

More directly, the record reflects that Defendants’ assertion misses the mark.

Dr. Rustgi testified that it is generally accepted that NDMA causes liver damage and

liver tumors, and that this is the “preponderance of the evidence going back

decades.”239 With respect to ranitidine, Dr. Rustgi opines that “exposure to NDMA

from ranitidine can cause the development of liver cancer.”240 Dr. Rustgi’s Bradford

Hill analysis, which he conducted, supports this opinion.241

This Court will not inject itself into a dispute over which party has the better

236 Minner, 791 A.2d at 841. 237 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 117 (emphasis added). 238 644 F.Supp.3d at 1258–59. 239 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 139 (citing Ex. 141, at 332:1–10, 331:1–2). 240 Id. (citing Ex. 53, at 35). 241 Id. (citing Ex. 141, at 331:9–18); In re Roundup, 390 F.Supp.3d at 1150–51. 49 science.242 Defendants’ quarrel with Dr. Rustgi’s reading of the Wang study is also

unavailing, as the balance of Defendants’ challenges to admissibility sound in areas

reserved in the first instance to the expert witness’s discretion and, ultimately, the

jury’s wisdom (i.e., cherry picking evidence, improper rejection of relevant data,

vagueness in describing methodology, inconsistent testimony, etc.)243 These issues

present a classic battle of the experts. Resolution of those disputes lies with the jury.

Defendants have failed to satisfy the Daubert requirements to exclude Dr.

Rustgi. The Motion is DENIED.

5. Dr. Ioannis Hatzaras

Plaintiffs identified Dr. Ioannis Hatzaras to evaluate whether NDMA

exposure from ranitidine can cause esophageal, stomach and colorectal cancer.244 In

conducting his evaluation, Dr. Hatzaras reviewed studies “demonstrating that

NDMA is a carcinogen” and reviewed “clinical studies looking into the relationship

between ranitidine containing NDMA. . . and development of foregut/colorectal

242 See McCullock, 61 F.3d at 1038; Karlo, 849 F.3d at 83 (“The question of whether a study’s results were properly calculated or interpreted ordinarily goes to the weight of the evidence, not to its admissibility”) (citation omitted); In re Roundup, 390 F.Supp.3d at 1150–51 (“different interpretations of [carcinogenicity] studies are not necessarily evidence of unreliability…plaintiffs may raise their concerns via cross-examination.”). 243 See Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 116–22; compare Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 139–46. 244 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 149; Ex. 194, at 1. 50 cancer.”245 Dr. Hatzaras “examined 36 particular studies in detail in his report. . .

and catalogued [their] strengths and weaknesses over 30 pages.”246 His report

“dissect[s] each study’s merits and drawbacks” to understand whether any

association is, in fact, causal.247

Upon completing his review of the literature, Dr. Hatzaras performed a

Bradford Hill analysis.248 He then conducted a separate Bradford Hill analysis for

esophageal, gastric, and colorectal cancer.249 Based on his review, evaluation and

analyses, Dr. Hatzaras concludes to a “reasonable degree of scientific certainty” that

“NDMA in ranitidine causes foregut/colorectal carcinoma.”250 His Bradford Hill

analysis confirms that opinion. Dr. Hatzaras’ analysis supports admissibility of his

opinion.251 Defendants present several challenges, notwithstanding.

Relying again on the MDL Order, Defendants contend that Dr. Hatzaras

employed “an inconsistent, results-driven approach” that “turn[s] science on its

head,” cherry picked his data, altered his opinion “mid-way through his deposition,”

245 Id. 246 Id. 247 Id. at 149–50. 248 Id. at 150. 249 Id. 250 Id. 251 In re Asbestos Litig., 911 A.2d at 1204–06; see In re Roundup, 390 F.Supp.3d at 1150–51 (admitting expert opinion where the expert “conducted a literature review and evaluated the quality of each of the studies.”). 51 and applied flawed methods, or none through a “standardless” approach.252 For the

reasons previously stated, the Court is not bound by that ruling.

Moreover, Plaintiffs’ comprehensive presentation of Dr. Hatzaras’ testimony

sufficiently addresses Defendants’ challenges,253 including but not limited to an

explanation of the science behind Dr. Hatzaras’ rejection of the “binary approach to

statistical significance extolled” by Defendants.254 Defendants’ arguments may

undermine Dr. Hatzaras’ opinion and be fodder for cross examination, but they

cannot exclude that opinion. These expert battles are to be fought before the

factfinders. This Motion is DENIED.

6. Dr. Dan J. Raz

Dr. Dan J. Raz, a thoracic surgeon and scientist specializing in lung cancer,

was asked by Plaintiffs to give opinions as to the causal relationship between

ranitidine and lung cancer.255 As with all of Plaintiffs experts, Defendants do not

challenge Dr. Raz’ qualifications to offer the opinion sought.256

Dr. Raz used a “comprehensive review of electronic databases to provide

sources for his opinions. He also looked to public health authorities, including the

252 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 76–78. 253 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 150–62. 254 Id. at 151–52. 255 Id. at 163. 256 See id. at 163–64 (detailing recitation of Dr. Raz’ CV). 52 FDA, WHO, and IARC. He carefully considered the strengths and weaknesses of

each source.”257 Upon completing his review, Dr. Raz performed a Bradford Hill

analysis to determine whether ranitidine causes lung cancer. He opined that

“NDMA exposure from ranitidine use is capable of causing lung cancer.”258

Dr. Raz’ methodology supports admission of his opinion.259 His

methodology appears to mirror that of Defendants’ lung cancer expert, Anil

Vachani, M.D., M.S.260 Though they reach different conclusions, “different

interpretations of these [sources] are not necessarily evidence of unreliability[.]”261

This is, literally, a battle of the experts.

Nonetheless, Defendants advance several challenges to Dr. Raz’ opinion.

They begin with the charge that his opinions are not generally accepted.262

Defendants conflate acceptance of methodology with acceptance of expert

conclusions.263 As noted above, while Daubert gives great latitude to the gatekeeper

in evaluating what factors may be implicated in these disputes, none of those

factors—including general acceptance of medical conclusions—is determinative in

257 Id. at 165. 258 Id. at 164–65. 259 See In re Asbestos Litig., 911 A.2d at 1205–06; In re Roundup, 390 F.Supp.3d at 1102. 260 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 165 n.614. 261 In re Roundup, 390 F.Supp.3d at 1150. 262 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 166. 263 See Daubert, 509 U.S. at 580; Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 166. 53 the trial court’s analysis. Indeed, Daubert holds that methods, not conclusions, are

to be tested.264 Each factor is but one among many that this Court may consider.

Importantly, Plaintiffs’ experts point to several public, private, and

governmental medical and regulatory entities that have studied NDMA and

concluded that NDMA is capable of causing cancer in humans. The record suggests

that GSK conceded as much in 2019.265 Also, the Wang study specifically showed

a “statistically significant association between exposure to ranitidine and lung

cancer.”266 The Habel study found an “overall increased cancer risk,” but fell just

short of statistical significance for lung cancer. But a positive association may still

be relied upon by experts; Daubert does not preclude it. It permits it.267

Defendants’ remaining challenges echo those cited in other expert challenges

discussed above, such as improper weighing/cherry picking studies on which to rely,

reliance on NDMA dietary studies, failing to consider/elevating Defendants’ science

over the witnesses. For example, Defendants complain that Dr. Raz’ opinion should

264 Daubert, 509 U.S. at 580; see Tumlinson, 81 A.3d at 1272 (noting that “an expert may also rely on techniques that have gained widespread acceptance in the scientific community.”) (emphasis added). 265 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 12, at 16:1–17 (“[P]rotect the scientists and anybody handling” NDMA in the laboratory.) (emphasis added); see also Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 11. 266 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 169; Ex. 146, at 119:7– 8. 267 Barrera, 2019 WL 2331090, at *5 (permitting expert to testify where opinions were based on some studies showing statistically significant associations or positive associations). 54 be excluded because he improperly weighed seven epidemiological studies on

ranitidine and lung cancer, and that his analysis of the studies was flawed.268 In his

report and deposition, Dr. Raz went into detail explaining that he considered all

seven of the studies and his reasons for giving more weight to two of them: Wang

and Habel.269

Yet, Defendants offer a one-page challenge to Dr. Raz’ Bradford Hill analysis

on three points: consistency, temporality, and strength of association.270

Defendants claim that the analysis is “unreliable’ because he relied upon only two

data points cited in those two studies of Wang and Habel. As discussed previously,

Dr. Raz’ reliance upon these studies is reasonable. Any quarrel with the application

of his methodology is for the fact finder.271

Evaluation of Bradford Hill factors turns on the “expert’s judgment in

selecting and weighing her sources.”272 “[E]xperts operating on reliable scientific

268 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 59–62. 269 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 167–71. 270 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 62–63. 271 Karlo, 849 F.3d at 83 (“The question of whether a study’s results were properly calculated or interpreted ordinarily goes to the weight of the evidence, not to its admissibility”); see also In re Roundup, 390 F.Supp.3d at 1150–51 (“different interpretations of [carcinogenicity] studies are not necessarily evidence of unreliability…plaintiffs may raise their concerns via cross-examination.”). 272 Barrera, 2019 WL 2331090, at *4. 55 principles could weigh the studies differently[.]”273 Any disputes about those

judgments are not for the Court to resolve. These decisions, made within the

framework constructed by Daubert and progeny, are reserved to the jury. Therefore,

Defendants’ Motion as to Dr. Raz is DENIED.

7. Dr. Pablo Leone

Dr. Leone is expected to offer a general causation opinion as to whether

NDMA exposure from ranitidine causes breast cancer based upon the

epidemiological evidence.274 Defendants do not challenge Dr. Leone’s

qualifications.275 To answer the general causation question, Dr. Leone reviewed the

“available scientific evidence regarding, Zantac (ranitidine) and NDMA”276 He used

a method “consistent with what is followed by cancer research scientists when

evaluating whether a chemical agent is a carcinogen and whether individuals are at

risk of developing cancer based on exposure.”277 His methodology involved:

• a review and evaluation of extensive medical scientific literature, including epidemiological, in vivo animal, in vitro studies and reviews of all relevant topics;

• research on publicly available information related to ranitidine and NDMA, their safety and association 273 Id. at *8. 274 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 200. 275 See id. at 200–04 (providing summary of Dr. Leone’s credentials). 276 Id. at 203. 277 Id. 56 with cancer generally via articles and references from Dr. Leone’s personal library of journals and textbooks, as well as PubMed and other relevant literature searches;

• a review and analysis of publications from scientific and governmental agencies, including WHO, IARC, FDA, and the EPA. and,

• a review and analysis of documents produced by Defendants in this litigation.278

Dr. Leone then assessed the totality of the evidence using a weight of the

evidence methodology in the context of Bradford Hill and different etiology

concepts, where he concluded to a reasonable degree of medical and scientific

certainty that “Zantac/ranitidine can cause breast cancer in humans, [and that] the

causal association is strongest for invasive ductal carcinoma.”279 Dr. Leone’s

methodology tracks that of many of the experts herein, including Defendants’ lung

expert, Anil Vachani.280

As noted, application of this methodology generally supports the admissibility

of the opinions at issue.281 To overcome this presumption, Defendants assert four

challenges to Dr. Leone’s opinion beyond the mechanics of the methodology: (1) his

278 Id. at 203–04. 279 Id. at 204. 280 Id. at 165. 281 See In re Asbestos Litig., 911 A.2d at 1204–06; In re Roundup, 390 F.Supp.3d at 1150–51 (admitting expert opinion where the expert “conducted a literature review and evaluated the quality of each of the studies.”). See also Barrera, 2019 WL 2331090, at *14, 17. 57 conclusions are not generally accepted;282 (2) he cannot explain the formulation of

his opinion;283 (3) he committed “several methodological errors that are red flags

under Daubert,” such as ignoring the principle of statistical significance and

applying an inappropriate substitute;284 and (4) he perform[ed] an “unreliable

Bradford Hill analysis.”285 The Court addresses these briefly, seriatim.

General acceptance. In considering this issue, one must bear in mind that the

Daubert analysis, rejecting the general acceptance requirement, focuses on “the

principles and methodology used in formulating an expert’s testimony, not the []

resulting conclusions.”286 Defendants assert that Dr. Leone concedes no other

agency or government has concluded that ranitidine can cause breast cancer and that

Dr. Leone has made “an analytical leap from available data that no other scientist

outside this litigation has made.”287 Not so. In the findings of the Mathes study,288

the authors reported a “2.2-fold increased risk of ductal type breast cancer,

representing a 120% increase in the risk of developing breast cancer associated with

Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ 282

Op. at 41. 283 Id. 284 Id. at 43. 285 Id. at 46. 286 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 205 (quoting Bowen, 906 A.2d at 794). 287 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 41 (quoting In re Zantac, 644 F.Supp.3d at 1187). 288 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 205 n.757; Ex. 117. 58 current use of ranitidine.”289 Therefore, the general acceptance argument does not

advance Defendants’ cause.

Second, Defendants argue that Dr. Leone cannot explain how he formulated

his opinion. Yet, he testified that he did not ascribe an individual weight to each

element of his data set, but instead that all of the data “informed [his] opinion.”290

Dr. Leone’s notes on the strengths and weaknesses of each study were taken into

account in his Bradford Hill analysis.291 He lays out in detail the various bases for

his opinion.292 To the extent Defendants dislike the explanations, they can present

their protestations to a jury.

Defendants also give a short shrift to Dr. Leone’s reference to the Braunstein

study, asserting that it has not been “subject to the rigors of peer-review.”293

Although Braunstein was posted on a pre-print online database, the underlying

epidemiological data in the study had already been peer-reviewed.294 The effort to

get the Braunstein study published does not impact the admissibility of Dr. Leone’s

289 Id. 290 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 41 (quoting Dr. Leone’s Tr.). 291 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 206; Ex. 155, at 23. 292 See id. at 206. 293 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 42. 294 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 206; Ex. 113, Ex. 142, at 8–9. 59 opinion, especially since general acceptance is not a requirement under Daubert.295

Moreover, the reasonableness of Dr. Leone’s reliance on Braunstein is for the jury’s

consideration.

Defendants’ challenges to Dr. Leone’s opinion assert also that he “cherry-

picks” favorable evidence, fails to consider contrary evidence,296 and ignores the

principle of statistical significance.297 These allegations have been held repeatedly

to be reserved for cross examination.298 Moreover, Plaintiffs rebut each of these

allegations.299 At this early stage, there is more than enough evidence to overcome

Defendants’ challenge to Dr. Leone’s formulation of his opinion.

Defendants’ final challenge is that Dr. Leone has performed an unreliable

Bradford Hill analysis.300 They assert Dr. Leone’s consistency conclusion is

unsupported, as the studies are noteworthy for their “consistent finding of no

295 See id. at 206–07. 296 Id. at 208–09. 297 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 43. 298 See Karlo, 849 F.3d at 83 (“The question of whether a study’s results were properly calculated or interpreted ordinarily goes to the weight of the evidence, not to its admissibility”); see also In re Roundup, 390 F.Supp.3d at 1150–51 (“different interpretations of [carcinogenicity] studies are not necessarily evidence of unreliability…plaintiffs may raise their concerns via cross- examination.”). 299 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 208–11. 300 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 46. 60 statistically significant association.”301 They declare his dose-response analysis

“unscientific” in part due to his failure to use the “generally accepted definition of a

“dose-response study.”302 They further reject Dr. Leone’s explanations defending

the applications and conclusions drawn on this issue, including his inability to

identify any threshold dose of exposure.303 Delaware law does not impose a bright

line threshold dose requirement, as discussed above. Moreover, none of these

challenges rises above the credibility-oriented questions that Daubert and progeny

for years have reserved to the jury. Defendants’ Motion as to Dr. Leone is DENIED.

8. Dr. Vitaly Margulis

Dr. Margulis has been asked to opine on whether it is likely that the NDMA

in ranitidine can cause cancer.304 Defendants do not challenge Dr. Margulis’s

qualifications.305 Dr. Margulis reviewed publicly available literature on ranitidine,

NDMA and renal cancer, including both primary studies and “publications from

scientific and governmental authorities, such as WHO, TARC, FDA and others.306

In his report, Dr. Margulis discusses how ranitidine breaks down into NDMA

301 Id. 302 Id. 303 Id. at 47, 47 n.85. 304 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 212. 305 See id. (providing Dr. Margulis’ professional education and practice). 306 Id. at 213. 61 and the mechanism by which NDMA can cause cancer.307 Relying on in vitro and

animal studies, he explains that, in the human body, NDMA metabolizes into “DNA

adducts,” which induce “carcinogenic point mutations.”308 Based on his review, Dr.

Margulis concludes that NDMA is a “potent carcinogen in every species tested” at

“single doses and after long-term exposure to smaller doses.”309 The animal studies

found animals were particularly likely to develop kidney tumors.310

Dr. Margulis then analyzed ranitidine-specific epidemiology. Six studies

reported a kidney cancer result.311 He analyzed each, finding some strong and others

seriously flawed.312 Overall, Dr. Margulis found that every study had “non-

differential misclassification of exposure” which “likely biased risk estimates

toward the null;” that is, the studies “were particularly likely to report a false

negative result.”313 In Dr. Margulis’s expert opinion, none of the epidemiological

studies could measure “important data points,” which led to “limitations” impossible

to overcome.

After consideration of the literature, Dr. Margulis conducted a Bradford Hill

307 Id. 308 Id. 309 Id. at 213–14. 310 Id. at 214. 311 Id. 312 Id. 313 Id. 62 analysis, which led him to opine that “the NDMA in ranitidine can cause cancer.”314

Thereafter, Dr. Margulis authored a peer-reviewed article describing the background

of NDMA and ranitidine and proffering—as a specific mechanism for

carcinogenesis—his conclusions as to the harmful metabolization of NDMA.315 The

mechanism is based on human in vitro studies and animal studies.316

In both his expert report and his peer-reviewed article, Dr. Margulis “explains

that animal and in vitro studies can be applied to humans. . . based on the similarities

in NDMA metabolism seen in animal studies and in vitro human cellular

experiments.”317 Dr. Margulis included in his article ranitidine epidemiological

studies, including the same criticisms he raised in his expert report, one of which

noted that “any conclusions drawn from these observational studies, whether

supporting or challenging. . . should be interpreted with caution.”318

Defendants challenge Dr. Margulis’s opinion much as they have many of the

others; he is inconsistent in his approach to statistical significance;319 his conclusion

314 Id. at 215. 315 Id. at 215–16. 316 Id. at 216. 317 Id. (internal quotation marks omitted). 318 Id. (emphasis omitted). 319 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 50. 63 is not accepted by the scientific community;320 he “cherry-picks” his evidence;321

and his “principal” reliance on dietary and worker NDMA studies is not

appropriate.322

The extended discussion of Dr. Margulis’s methodology and findings make

plain the detailed nature of his statistical analysis.323 He is not a poseur.324

Defendants admit he is qualified to offer his opinion, and at this stage, his methods

confirm as much.

As to “principally” relying on NDMA dietary and worker studies, in his report

Dr. Margulis spends one paragraph each on dietary and occupational studies,

summarizing them, and emphasizes that the role those studies played in his

conclusion was “not significant.”325 He further considered the contrary statistical

findings in the six ranitidine studies.326 Plaintiffs emphasize that “[t]here is nothing

inconsistent about accurately reporting the actual results from these studies.”327

Defendants pause on these mixed results as “the definition of inconsistent

320 Id. at 49. 321 Id. at 50–53. 322 Id. at 53–55. 323 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 214, 217–19. 324 In re Asbestos Litig., 911 A.2d at 1207. 325 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 218. 326 Id. at 214, 217–18. 327 Id. at 217. 64 results,”328 although they point out Dr. Margulis’s conclusion that the six studies

broke evenly, three showing an increased risk and three a decreased risk. At this

level of science, any characterization of these numbers would do the data a

disservice. And asking this Court to do the math is not a good idea. Numerically,

the results, inconsistent or otherwise, do not tip the scale in either direction.329

Defendants further throw several accusations at Dr. Margulis’s report. While

the Court considers many herein, review of the Opposition gives a more fulsome

recitation of Dr. Margulis’ rebuttal in defense of his opinion.330 Some, Plaintiffs

suggest, mischaracterize his opinions.331 Some, they claim, ignore his testimony.332

These challenges, along with claims of cherry-picking and flawed reliance on certain

NDMA studies, fall victim to the wisdom of Daubert: they belong to the jury.333

The Motion to exclude Dr. Margulis’s opinion is DENIED.

9. Dr. George Miller

Plaintiffs have asked Dr. Miller to provide opinions regarding whether

328 See Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 51; Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 217. From a non-scientist’s perspective, that the six studies broke evenly on the point 3 to 3 does not seem to fit the definition of inconsistent. 329 Barrera, 2019 WL 2331090, at *17 (stating that opposing experts interpreted the same studies differently “does not render [their] opinions inadmissible.”). 330 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 216–21. 331 See, e.g., id. at 217–19. 332 Id. at 219. 333 Karlo, 849 F.3d at 83; In re Roundup, 390 F.Supp.3d at 1150–51. 65 NDMA exposure from ranitidine causes pancreatic cancer.334 Defendants do not

challenge Dr. Miller’s qualifications to opine on that question.335 Defendants would

exploit Dr. Miller’s lack of formal epidemiological training, but they have not voiced

objection to the expert’s qualifications to offer those opinions. Dr. Miller may testify

on epidemiological issues implicated in his report.336

Dr. Miller is expected to opine within a reasonable degree of medical certainty

that there is a causal link between ranitidine and pancreatic cancer.337 In preparing

that opinion, Dr. Miller first analyzed “whether ranitidine contains a cancer-causing

agent” and—relying in part on GSK’s root cause analysis—found that NDMA is a

toxic degeneration byproduct of ranitidine.338 Dr. Miller also relied upon testing

outlined in the expert report by Emery Pharma.339 He analyzed studies that showed

a link between dietary sources and pancreatic cancer. Dr. Miller then compared the

studies with others that did not show an association between ingestion of nitrates and

pancreatic cancer, finding serious flaws with those that did not show an

association.340

334 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 184. 335 See id. at 185–87 (providing summary of Dr. Miller's educational and professional background). 336 See Barrera, 2019 WL 2331090, at *13. 337 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 187. 338 Id. 339 Id. at 187–88. 340 Id. at 188. 66 Dr. Miller also analyzed studies showing a link between occupational

exposure to NDMA and pancreatic cancer, and weighed the strengths and

weaknesses of each study to determine if the peer-reviewed studies supported such

a link. Dr. Miller then analyzed peer-reviewed studies regarding the link between

NDMA exposure from ranitidine use and pancreatic cancer. After weighing the

strengths and weaknesses of each study, Dr. Miller then analyzed the Bradford Hill

criteria, and concluded the existence of a causal link between ranitidine and

pancreatic cancer.341 And added that “[t]here is considerable biologic plausibility to

support this conclusion and lend support to the well-conducted human

epidemiological studies.”342

Defendants argue that Dr. Miller’s methodology is unreliable. Pointing to a

number of alleged deficiencies across the breadth of his opinion, the gist is that the

augmentation of his opinions are evidence of the “results-oriented nature of his

analyses.”343 These allegations do not support exclusion of his opinion.344 Nor does

what Defendants characterize as Dr. Miller’s “inconsistent application of power and

341 Id. at 189. 342 Id. 343 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 63. 344 Barrera, 2019 WL 2331090, at *11 (changing opinion goes to the weight, not admissibility). 67 follow-up to the studies.”345 Their rejection of his analysis and application of follow-

up time,346 does not compel exclusion. Likewise, the arguments that Dr. Miller made

a “faulty assumption” and improperly “flipped the burden” of proof,347 or turned

“limitations in the ‘negative’ studies into strengths in the studies he preferred,”348 go

to weight, not admissibility.349

In a broader attack, Defendants accuse Dr. Miller of providing no

methodology for how he evaluated studies. First, this claim is rebutted by the

extensive background review Dr. Miller performed as part of his preparation. Miller

testified that he “conducted a systematic review of the literature and evaluated the

science to arrive at his conclusions.”350 Second, Dr. Miller dedicates eleven pages

of his report discussing the various studies and their strengths and limitations.351

345 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 93–94; see Reply Brief in Support of Brand Defendants’ and Patheon’s Motions to Exclude: (1) Plaintiffs’ General Causation Experts’ Opinions; and (2) Dr. Charles Jameson, Trans. ID 71797654 (Jan. 12, 2024) (herein “Reply Br. in Supp. of Defs.’ Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. & Dr. Jameson”) at 63–64. 346 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 194–95; see Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 94– 95. 347 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 91. 348 Id. (emphasis in original). 349 McCullock, 61 F.3d at 1038; Karlo, 849 F.3d at 83. 350 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 91. 351 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 192. 68 Defendants accuse Dr. Miller of not ranking the studies by quality.352 But Dr.

Miller wrote extensively in his report regarding the strengths and weaknesses of each

study.353 They complain that Dr. Miller was not able to identify the key criteria he

used to determine a study’s reliability. Yet, he testified that the most critical factors

for him in evaluating studies were “median age to study an appropriate population

and follow-up time.”354 Defendants discredit Dr. Miller’s Bradford Hill analysis,

although he testified at length about same.355

Dr. Miller’s conclusions are reliable.356 At this stage, it cannot be said that

the scope of his review and the science used to formulate his opinions do not support

admissibility.357 Defendants may have succeeded at times in making this a close

call. But close calls go to the jury. The Motion to exclude his opinion is DENIED.

10. Bruce J. Trock, MPH, PhD

Dr. Trock has been disclosed to give general causation opinions regarding

whether NDMA exposure from ranitidine causes prostate cancer.358 Dr. Trock is a

352 Id. at 193. 353 Id. 354 Id. 355 See id. at 198–99. 356 Barrera, 2019 WL 2331090, at *14. 357 In re Asbestos Litig., 911 A.2d at 1205–06; In re Roundup, 390 F.Supp.3d at 1150–51 (expert opinion admitted where the expert “conducted a literature review and evaluated the quality of each of the studies.”); accord, Barrera, 2019 WL 2331090, at *14, 17. 358 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 174. 69 cancer epidemiologist at Johns Hopkins University, with 37 years of experience in

cancer research, 21 of which were focused on prostate cancer.359 He has authored,

or co-authored, over 320 peer-reviewed publications, 201 of which focus on prostate

cancer.360 Defendants do not challenge Dr. Trock’s qualifications to testify here.361

In preparing his opinions, Dr. Trock reviewed and analyzed “the entirety of

the relevant scientific and epidemiological literature concerning the association

between ranitidine and prostate cancer.”362 In doing so, Dr. Trock “assessed the

strength of the relevant evidence derived from animal and occupational studies, and

Dr. Trock used his review and analysis of the medical literature, including the

strengths and weaknesses of the pertinent studies, to perform a Bradford Hill

analysis.363 Based on his reviews and his Bradford Hill analysis, Dr. Trock

concluded, to a reasonable degree of scientific certainty, that exposure to ranitidine

can cause prostate cancer in humans.364 His opinions are based on sound, reliable

scientific methodology, and are generally admissible.365

359 Id. 360 Id. 361 See id. at 174–75 (providing a more complete summary of Dr. Trock’s qualifications). 362 Id. at 175; Ex. 147, at 24–38. 363 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 175. 364 Id. at 176. 365 Id.; see In re Asbestos Litig., 911 A.2d at 1205–06; see also In re Roundup, 390 F.3d at 1150– 51 (expert opinion admitted where the expert “conducted a literature review and evaluated the quality of each of the studies.”); accord, Barrera, 2019 WL 2331090, at *14, 17. 70 Defendants interpose several challenges to that admissibility. Their initial

challenge argues that relevant epidemiological studies “reported no statistically

significant positive associations between ranitidine use and prostate cancer.”366

Plaintiffs counter that, in fact, Dr. Trock noted that of the nine relevant

epidemiological studies concerning ranitidine, three actually observed “increases in

the incidence of prostate cancer.”367 Dr. Trock further distinguished five of the

remaining six studies as considerably flawed (i.e., they used inadequate follow up

periods, had short durations of exposure to ranitidine, and failed to adjust for

potential confounders).368 Several studies “lacked data on duration or cumulative

dose of ranitidine, and recorded only at baseline,” and were therefore susceptible to

misclassification.369

Defendants first reject Dr. Trock’s analysis and conclusions. That is, of

course, their prerogative, but does not support exclusion. Similarly, Defendants

raise again the charge that his opinion is inadmissible because his conclusions are

not generally accepted in the medical community.370

366 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 64. 367 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 177. 368 Id. 369 Id. 370 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 64–65. 71 As noted, Daubert rejected the general acceptance requirement. Defendants

nonetheless urge that general acceptance is still an indicator of unreliable

methodology.371 But, the record establishes that Dr. Trock analyzed the relevant

data, and his opinions align with three of the relevant studies. This evidence is to be

used flexibly when evaluating reliability. Again, Daubert does not charge the trial

court to pick one expert’s science over another’s.372

Defendants next argue that Dr. Trock’s conclusions are unreliable because he

“ignores epidemiological ranitidine studies and takes the novel approach of drawing

conclusions about ranitidine based on studies” of rubber workers and animals.373

Defendants point to the MDL Order and its rejection of the Hidajat study as

flawed.374 Those may have been appropriate conclusions for that court to draw. But

as presented through these experts, in Delaware, it is not the role of this Court to

substitute its scientific conclusions for those of an expert scientist.

Dr. Trock analyzed the Hidajat study and compared it to a second rubber

worker study, which he rejected as marred by speculation.375 Dr. Trock did not rely

371 Id. at 65. 372 In re Asbestos Litig., 911 A.2d at 1207. 373 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 65–67; Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 179. 374 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 66. 375 Id. 72 on animal studies alone. He considered their import along with his evaluation of the

six epidemiological studies available. Defendants acknowledge that Dr. Trock

analyzed the epidemiological ranitidine studies and dismissed them as “severely

flawed.”376 That approach is consistent with the proper methodology applied in such

circumstances.377 Delaware law “does not require that evidence of general causation

take the form of epidemiological evidence . . . Evidence such as animal studies, in

vivo studies, in vitro studies, toxicology, and case studies can be used to show

causation.”378 These factors are to be applied flexibly.379

Defendants’ final charge is that Dr. Trock’s Bradford Hill analysis is

unreliable.380 They argue that an expert must address epidemiological evidence that

is inconsistent with his opinion.381 As discussed above, Dr. Trock did that. Their

argument about dose response, which is another of the Bradford Hill criteria that

may be considered, does not suffice to compel exclusion of Dr. Trock’s opinion.

376 Id. at 65–66. 377 See, e.g., Barrera, 2019 WL 2331090, at *14. 378 Id. 379 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 182 (discussing Dr. Trock’s selection of studies on which he relied); see, e.g., id. (“Dr. Trock’s analysis, placing more weight on NDMA occupational [and animal] studies, is entirely reasonable in light of the significant limitations in the nine epidemiological studies of ranitidine.”); see also id. at 180 (discussing Dr. Trock’s use of animal studies, emphasizing that “in considering the weight of the evidence, Dr. Trock considered NDMA animal studies - but not to the exclusion of the relevant epidemiological literature.”). 380 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Pls.’ Gen. Causation Experts’ Op. at 68–69. 381 Id. at 69. 73 Defendants can take up these challenges before the jury. The Motion to exclude Dr.

Trock is DENIED.

11. Emery Pharma

Plaintiffs retained Emery Pharma (hereinafter “Emery”) to “conduct further

testing on the levels of NDMA in ranitidine provided by Defendants and specifically

the levels in Plaintiffs’ own pills and opine on the nature of ranitidine’s ability to

degrade and transform into NDMA.”382

Emery is a “full-service contract research laboratory, specializing in

analytical, bioanalytical chemistry, microbiology and cell biology services, custom

synthesis, [] general research and development and [] the standards employed in the

manufacture of drugs, not in research.”383 Defendants characterize Emery as a

“litigation support lab.”384 Emery counters that “only approximately twenty percent

of Emery’s revenues are from litigation consulting.”385 Emery describes the

majority of its clients as pharmaceutical companies that reach out to Emery for

“isolation characterization work;” that is, to analyze and identify “an impurity in a

382 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 223. 383 Id. at 224. 384 Brief in Support of Brand Defendants’ and Patheon’s Motion to Exclude Plaintiffs’ Expert, Emery Pharma, Trans. ID 71408808 (Nov. 15, 2023) (hereinafter “Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma”) at 14 n.23. The Court notes Defendants’ Brief to Exclude Emery Pharma is devoid of pagination, as such the Court references the corresponding PDF page numbers. 385 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 221 n.829. 74 drug that is being marketed.”386

Defendants do not challenge Emery’s qualifications to render the opinions

requested of it.387 Yet, the parties devote nearly 150 pages of briefing to the

admissibility of the Emery opinion alone. The somewhat more aggressive and

pejorative rhetoric in the briefs suggests the Emery opinion lies at the heart of the

Daubert debate, for both sides.

Defendants offer nine challenges to the admissibility of the Emery Opinion:

(1) Plaintiffs’ use of HILIC methodology is unvalidated and unreliable;

(2) Plaintiffs’ opinion of manual integration, without proper protocols, is unreliable;

(3) Plaintiffs failed to keep proper documentation;

(4) Dr. Najafi left all operational decisions in the testing process to the discretion of his assistants, who did not follow preset protocols;

(5) the Emery opinion has not been published or submitted for peer review;

(6) the Emery opinion does not “fit” the parameters of the issue here;

(7) Emery’s simulated studies fail to meet the Daubert standards;

386 Id. 387 See id. at 224–28 (providing a more complete recitation of Emery qualifications and its representatives). 75 (8) Emery’s simulated gastric fluid study is not reliable; and

(9) Emery’s “miscellaneous tests” do not “fit” the case and are not reliable.388

The Court addresses briefly each of Defendants’ challenges separately. The

Court prefers not to get into the weeds of the science, but some digging is required.

a. Emery’s Use of HILIC

Emery used Hydrophilic Interaction Chromatography (“HILIC”) to test for

the presence of ranitidine. Defendants argue that HILIC is unvalidated, and

therefore unreliable. Defendants also charge that the increased measure of ranitidine

when HILIC was used supports their charge that HILIC’s use was a litigation-driven

decision, made to skew the numbers in Plaintiffs’ favor.

HILIC is a technique for separation of polar compounds. Plaintiffs explain

that HILIC was used in the first part of Emery’s separation processes “to improve

sample identification and quantification.”389 Plaintiffs further indicate that Emery’s

method known as LC-MS/MS (the combination of liquid chromatography (“LC”)

and mass spectrometry (“MS”)) “uses the same underlying technology the FDA

used, with the difference being the type of initial column used for separation of the

388 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 21–22. 389 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 236. 76 analyte.”390

Plaintiffs further assert that HILIC is a well-established, accepted column for

use in chromatography with polar compounds, which NDMA is.391 They quote from

a monograph by Defendants’ expert, Bernard Olsen, in support:

The popularity of [HILIC] has grown rapidly in recent years. The HILIC mode can provide retention and separation of polar compounds that are difficult to analyze by reversed-phase high-performance liquid chromatography (RPLC) or other means. HILIC has been utilized in a variety of applications including drugs and metabolites in biological fluids, biochemicals, pharmaceuticals (from drug discovery to quality control), foods and environmental.392

The Olsen monograph notes that HILIC “can be particularly suited in the

determination of specific impurities, including polar compounds,”393 of which

NDMA is one.

Emery explains its reasons for preferring HILIC columns over reverse-phase

columns.394 Emery also showed that its protocol, including use of an HILIC column,

was “fully validated.”395 Notably, the JCCP court rejected this same Daubert

390 Id. 391 Id. at 237. 392 Id. 393 Id. at 237, 237 n.878. 394 Id. at 236–38. 395 Id. at 239. 77 challenge.396 Emery’s efforts notwithstanding, Defendants reject their science and

stand on the MDL Order.397 Following Delaware jurisprudence, this Court finds that

HILIC has been validated and determined reliable, and its use in measuring

ranitidine constitutes sound methodology to survive a Daubert challenge.

b. Manual Integration

Defendants’ challenge of Emery’s use of manual integration involves data

integrity. They claim Plaintiffs did not follow a Standard Operating Procedure

(SOP) to guide when “analysts perform manual integrations.”398 They further accuse

Emery of performing manual integrations “unreliably, arbitrarily, and following no

set standards.”399

Emery explained that “all decisions regarding when and how to conduct

manual integrations, along with the integrations themselves, were done using the

same scientific principles as written in Emery’s Standard Operating Procedure

(“SOP”) for chromatography analysis [] that was in effect at the time.”400 It appears

396 Id. at 254; see also Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 75, at 2 3. 397 Brand Defendants’ and Patheon’s Reply in Support of their Motion to Exclude Plaintiffs’ Expert, Emery Pharma (herein “Defs.’ Reply Br. in Supp. of Mot. to Exclude Emery Pharma”) at 9–11. 398 See Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 29. 399 Id.; Ex. 15, at 1. 400 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 241. 78 that Defendants’ expert, Dr. Olsen, also relied on the same scientific principles.401

“[W]hether performed automatically or manually. . . integration must be

scientifically justifiable.”402 Defendants concede that an “analyst must exercise

professional judgment in deciding when use of a manual integration is

appropriate.”403 Emery performed manual integrations only when the default

integration was scientifically unsound.404 To the extent that Defendants rely on the

Agilent monograph in support of this argument, this Court accepts the reasons set

for by Plaintiffs that any data manipulation that was focused on FDA compliance is

not at issue here.405

Defendants further argue that Emery “left manual adjustments to the

unfettered discretion of its staff,” and that performing manual engagements “may”

be a sign of a “flawed method.”406 For several reasons, this argument is insufficient

to warrant relief.

Emery makes the point that “Dr. Cheu,” one of the primary representatives of

Emery on the opinion, “did these manual integrations.”407 In their Reply, Defendants

401 Id. 402 Id. at 240. 403 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 29. 404 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 240. 405 Id. at 255–56. 406 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 30 (quoting In re Zantac, 644 F.Supp.3d at 1123)) (emphasis added). 407 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 240–41. 79 equivocate on this point while doubling down: “Emery allowed its analysts,

including Dr. Cheu, to perform manual integrations in their sole judgment and

discretion.”408 Further, Dr. Najafi testified that he supervised the work being done

at Emery and double-checked the work being done by his staff scientists to make

sure [he was] confident of the numbers.”409 Dr. Najafi reviewed the lab results, the

lab notebooks, and synthesized that data in formulating his opinion.410

Manual versus electronic integration turns on the scientist’s assessments of

the accuracy and utility of each in a particular circumstance. As the discussion

illustrates, these are complicated questions well beyond the wisdom of this trial

judge, who, consistent with Daubert and its progeny, will not pick a winner. The

answer rests with the jury.

c. Lack of Documentation of Lab Results

Defendants allege that Plaintiffs’ protocols and test results fail the reliability

requirement of Daubert due to their failure to “describe the methods they used as

fully and accurately as possible.”411 Defendants emphasize that “[w]ithout

408 Defs.’ Reply Br. in Supp. of Mot. to Exclude Emery Pharma at 12. 409 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 260. 410 Id. 411 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 32 n.51; see also id. Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma Ex. 35, at 48. 80 documentation the process is meaningless; essentially there has been no study.”412

The initial challenge focuses on Emery’s failure to adequately document its

testing.413 In response, Plaintiffs have sufficiently explained that Emery designed

and created protocols for each experiment, each of which was validated and the

results of that validation produced.414 Plaintiffs add that, beyond those “standalone

validations, each analytical run includes a series of calibrations and quality control

injections to further validate the process in run,” and each test “was documented in

a lab notebook contemporaneously maintained by the analyst conducting the

experiment and counter signed by “another researcher who validated the

experiment.”415

Defendants next attack Emery’s lack of protocols for baseline testing,

emphasizing that “none was ever created.”416 The straight-forward response is that

that “Emery’s task regarding baseline testing [] was simply to determine what levels

of NDMA were detectible, if any, in the pills and API [active pharmaceutical

ingredients] produced to Plaintiffs by Defendants. There was no hypothesis to be

tested. There was no need for a ‘study design’ outside that of testing protocol and

412 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 32 n.51. 413 Id. at 35; Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 257. 414 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 256. 415 Id. at 256–57. 416 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 34 n.54. 81 method. Emery tested the pills and API and reported the results. . . .”417

As to the adequacy of the lab notebooks, Plaintiffs explain that “[m]ost raw

and processed data for LC-MS/MS simply cannot be recorded in lab notebooks, as

it is maintained electronically.418 The lab notebooks, however, “contain a reference

to exactly where on Emery’s system (by folder path) that data was stored.”419 All of

the written validated protocol, underlying raw and processed data from the conduct

of the testing was provided to Defendants in [the relevant] format, with printed

versions in the form of PDFs, and also stored electronically in the [relevant] system,

where it remains to this day, and all of it was produced to the Defendants.”420

Plaintiffs further indicate they provided Defendants with “all of [the test]

results along with the corresponding test names, lot numbers, etc., in Excel format,”

noting that Defendants can “conduct their own data analysis to come up with

whatever statistical calculations they wish,” something, Plaintiffs note, Defendants

have not done.421 If Plaintiffs failed to describe their methods as fully and accurately

as possible, any such failing is reserved as a topic for cross examination.422

417 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 257–58 (emphasis in original). 418 Id. at 257. 419 Id. 420 Id.; see Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 202. 421 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 258. 422 See, e.g., McCullock, 61 F.3d at 1043–44; Karlo, 849 F.3d at 81–84. 82 d. Dr. Najafi’s Reliance on the Work of His Team

Defendants take the position that Dr. Najafi, individually, should be excluded

because he relied “entirely” on the work of his team. They impugn Dr. Najafi with

the statement that he is “merely parroting” work done by others.423 Not so.

Dr. Najafi testified on his role in the preparation of Emery’s testing

conclusions.424 Defendants do not take that testimony on directly. Rather, they rely

on the MDL Order and deposition testimony that contradicts Dr. Najafi’s own

testimony. With that, they argue that Emery analysts conducted testing without

“guiding principles from Dr. Najafi” or without written procedures or instructions.425

They highlight the inclusion of three signatures on the Emery Report as “tacit

acknowledgement of his lack of firsthand knowledge.”426

The fact that several scientists signed the Report may be weighed as a

testament to each scientist’s involvement in its preparation, and their certification of

its accuracy and validity. Dr. Najafi’s testimony supports that conclusion. The

Defendants are free to argue that the actions of the signatories somehow implicate

Dr. Najafi. But not at this juncture. Their allegations on this score present a

423 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 40. 424 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 259–61. 425 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 39 (citing In re Zantac, 644 F.Supp.3d at 1138). 426 Id. 83 credibility issue for the jury.

e. Lack of Publication or Peer Review

Defendants cite lack of peer review or publication as a “pertinent

consideration” of whether a theory or technique is valid.427 At the outset, Defendants

offer no authority in support, beyond the MDL Order in Zantac.428 Moreover, the

lack of peer review or publication presents an issue for the jury. Nor is Emery’s

science an orphan child.429 And as previously mentioned, even Defendants’ expert,

Dr. Bernard Olsen, extolls the LS-MS/MS technique used by Plaintiffs.430 As

Plaintiffs’ point out, when Defendants’ experts were asked about publication, they

refused to suggest lack of publication as evidence of unreliability.431 If lack of peer

review or publication has any utility here, it is fodder for cross-examination, not

exclusion.

f. Emery’s Baseline Testing “Does Not Fit”

Defendants next challenge the so-called “fit” of Emery’s baseline testing to

427 Id. at 40. 428 Id. 429 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 261 (“[T]he use of LC-MS/MS to detect and quantify impurities in drug substances, and the methodology used to validate the specific protocol applied by Emery are both not only widely accepted and published in peer reviewed literature but have been available and in use for decades.”). 430 Id. at 237. 431 Id. at 262. 84 the facts of the case.432 The challenge rests on the premise that the amount of

ranitidine in active pharmaceutical ingredients (API) is different than in a pill that a

user ingests.433 Testing API alone, Defendants argue, “skews testing results high

and does not reflect what individuals actually ingest.”434 Plaintiffs argue that this is

a faulty premise via this explanation:

[N]one of the steps involved in creating the final dosage form . . . is supposed to change the included [active pharmaceutical ingredient] API. Thus, any NDMA contained in the API will be, perforce, also included in the finished pill. This is why, for example, GSK also tested and reported the NDMA in API when it conducted its root cause analysis.435

That is, “the NDMA contained in the API at the time the finished dose is

manufactured will get transferred to the pill itself.”436 Defendants do not counter

this analysis in their Reply. Emery’s testing of API fits the facts of the case and will

not be excluded.

g. Emery’s Simulated Environmental Tests

Emery conducted three “simulated consumer experience” tests to measure

432 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 41; see Daubert, 509 U.S. at 591. 433 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 41. 434 Id. 435 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 263. 436 Id. 85 how NDMA might form in ranitidine.437 Plaintiffs suggest the simulations show the

breakdown of ranitidine “into NDMA in various real-world scenarios, and produces

high levels of NDMA, [which is] relevant to Defendants’ argument that there is

minimal NDMA exposure from taking ranitidine.”438 Plaintiffs suggest that such

testing shows “that NDMA could reasonably form under specific instances—

instances that would apply to all plaintiffs.”439 Thus, their argument follows, the

simulations are relevant at the general causation stage.440 This Court agrees.

Defendants’ challenge to the simulations follows a common path. They each

begin with a general acceptance attack, which they support in the main with a

quotation from the MDL Order.441 Citing to that ruling, they argue that “no other

laboratory in the world has used these tests to measure drug stability; no agency

requires or recognizes them [;] [and no] paper has ever been published validating

their reliability.”442

As to the car simulation, Defendants note that “Emery did not study Zantac

stored in real-life cars,” instead making “a series of unsupported assumptions about

437 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 42. 438 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 263. 439 Id. 440 Id. 441 See Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 44 (quoting In re Zantac, 644 F.Supp.3d at 1150). 442 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 42. 86 consumer behavior and car conditions” to simulate that experience.443 They criticize

Dr. Najafi’s reliance on the Vanos 1028 study, and urge that “even if modeling an

experiment for a drug stability study. . . were a reliable methodology,” Emery’s car

simulation did not comport with such a model.444

But the Vanos report outlines three bases for its data—Vanos, Grunstein, and

the Assessment of the Common Carrier Shipping Environmental General Technical

Report.445 Defendants concede that Plaintiffs cited a few studies in support of their

data.446 And further concede they missed key data points from the Grunstein study

pertaining to the average air temperature used in the Emery study.447 As the several

cases repeatedly cited above make clear, such criticism goes to weight, not

admissibility.

Defendants lodge identical challenges to the bathroom simulation.448 As with

the car simulation, Defendants acknowledge the validation of the “non-peer

443 Id. 444 Id. at 43 (quoting In re Zantac, 644 F.Supp.3d at 1147). 445 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 264. 446 DEFAs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 42; Ex. 10, at 230:16–17. 447 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 264. 448 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 44 (“Emery’s ‘bathroom simulation’ studies did not test Zantac product in a real-world bathroom, but instead attempted to recreate the conditions of a bathroom based on a series of unsupported assumptions . . . [it] has nothing to do with drug stability or the effect that a bathroom environment could have on a drug product.”). 87 reviewed” Aizawa study, but they retrench by alleging that Plaintiffs departed from

the Aizawa model by using more “extreme conditions” than contemplated.449

Defendants also advance lack of general acceptance, and quote a near verbatim

repetition from the MDL Order to that end, just as they did with the car simulation.450

Yet, Defendants, again, missed a study relied upon by Plaintiffs that favors their

position.451

Plaintiffs’ last simulation created “climactic zones” to “simulate. . . common

consumer experiences with Zantac.”452 Defendants again stress that the climatic

zones on which they were based “were not designed to mimic real-world

conditions,” and, citing the MDL order in Zantac, argue that they were “designed to

increase the rate of chemical degradation or physical damage of a drug substance or

drug product by using exaggerated storage conditions[.]”453 Defendants also attack

the climactic zone testing’s reliability because, they say, “it departed from the actual

Zantac container closure system” and for its lack of support for the assumption that

a typical plaintiff or distributor stores ranitidine at 65 % relative humidity in an

outside, non-air conditioned environment.454

449 Id. 450 Id. at 46. 451 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 264–65. 452 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 45. 453 Id. (quoting In re Zantac, 644 F.Supp.3d at 1152) (emphasis in original). 454 Id. at 46. 88 That criticism appears to validate the testing, as Plaintiffs explained, “because

[as noted below] a laboratory cannot actually recreate months’ worth of exposure to

varied temperature and humidity conditions in the time frames involved with

testing.”455

“General causation considers the possibility that a certain exposure caused a

certain harm, not the likelihood that it did.”456 Plaintiffs designed the three

simulations to address a corollary point; that is, “that under the conditions tested,

which simulate real-world conditions, ranitidine breaks down to form NDMA, not

that the exact NDMA levels reported by Emery would be the levels reported by

Emery in any particular pill.”457

Throughout their briefing on the three simulations, Defendants rely

predominantly on the conclusions of the MDL Order. Plaintiffs challenge as

“missing the point” Defendants’ (and the MDL Order’s) overarching criticism of the

design of their simulations: “the entire purpose of stability testing is to see what

happens in exaggerated conditions because a laboratory cannot actually recreate

months’ worth of exposure to varied temperature and humidity conditions in the time

frames involved with testing.”458

455 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 265. 456 Barrera, 2019 WL 2331090, at *4 (quoting Tumlinson II, 2013 WL 7084888, at *4). 457 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 266. 458 Id. at 265. 89 These tests, like opinions—especially those evolving in response to an issue

that, it appears, science has not yet caught up with—depend on the “expert’s

judgment in selecting and weighing her sources.”459 Defendants reject Emery’s

science, including the decisions made in the design and execution of the simulations,

as exemplified by the container system debate: Plaintiffs say the system used in

their testing was proper. Defendants argue it was not. So it goes. But Emery’s

opinion, and testing, are “rooted in science” and therefore “scientifically reliable.”460

That is not to say they are unassailable. But, under these circumstances, the Court

cannot and will not declare one side’s science as reliable and cast off the other’s.461

This dispute is appropriate grist for the jury’s mill.462

h. Emery’s Simulated Gastric Fluid Test

Defendants’ attack on Emery’s Gastric Fluid tests regurgitates the criticism of

Emery’s other tests, discussed above. They are: lack of general acceptance, lack of

publication and peer review, improper and flawed assumptions, conclusions

contradicted by other literature, improper premises, testing did not track

hypothetical, and that the testing was results-oriented.463 For the same reasons

459 Barrera, 2019 WL 2331090, at *4; see Long, 2004 WL 1543226, at *1. 460 Barrera, 2019 WL 2331090, at *14, 17. 461 In re Asbestos Litig., 911 A.2d at 1207. 462 Id. 463 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 47. 90 previously stated, there is no need to indulge in an extended discussion of them. The

challenges go to weight, not admissibility.

i. Emery’s Miscellaneous Tests

On this challenge, Defendants concede at the outset that “these studies suffer

the same methodological issues as the testing” above.464 These challenges are

rejected, for the same reasons.

Defendants also assert that “these tests have no purpose or connection to the

facts of the case; i.e., they lack the requisite fit.”465 Not so.

1. WHO NAP Test. The Nitrosation Assay Procedure (“NAP” test),

developed by the World Health Organization (WHO) and the International

Association for Research on Cancer (IARC), “combin[ed] an agent with sodium

nitrite in simulated or real gastric fluid. . . to allow systematic comparisons between

compounds is assessing their ability to nitrosate.”466 The creation of NDMA via

nitrosation of ranitidine is very much a part of the analyses at issue here. The NAP

test fits the case. That the test may not “represent physiological conditions” goes to

weight, not admissibility.467

2. Simulated Gastric Fluid Testing. The Court has already addressed the

464 Id. at 51. 465 Id. 466 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 94. 467 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 52. 91 challenges to Emery’s primary Gastric Fluid Simulation. Defendants here challenge

“additional SGF studies” based on the conclusions Defendants draw from “some of

the experiments.”468 This challenge does not undermine the “fit” of the tests.

3. KSCN Testing. This test was performed to study the hypothesis that

potassium thiocyanate, an endogenous compound present in human gastric juice, can

promote nitrosation of NDMA moieties to form NDMA in the stomach. 469 This is

connected to the facts of this case, as nitrosation of NDMA is one of the processes

at issue in exposure.

4. Refrigeration Testing. This test was performed to confirm GSK’s claim

in its root cause analysis that storage at certain temperatures stops the formation of

NDMA in ranitidine.470 It is relevant to whether Emery’s storage of ranitidine

samples was a factor in the amount of NDMA found in baseline testing. 471 This

issue “fits” as it is connected to the facts of the case.

5. Morphology Study. This challenge is more about challenges to the

construct of and assumptions behind the test than “fit.”472 That said, Plaintiffs

defend the test as intended to determine the accuracy of Defendant GSK’s hypothesis

468 Id. 469 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 267. 470 Id. 471 Id. 472 See id. at 266. 92 regarding rate of degradation of higher bulk density active pharmaceutical

ingredients (API,) compared to other API. This test is relevant to degradation and

to any attempt by GSK to “portray its API” as “superior or more resistant than other

sourced API.”473

6. Content Uniformity Test. Defendants again target Emery’s handling of

the tests, and their conclusions, more than “fit.”474 Plaintiffs defend the test as

“showing that the testing of single pills from a container would be generally

representative of the levels of NDMA to be found in the ranitidine container.”475

This test “fits,” given the issue joined on the proper container to be used preparing

opinions on degradation.

7. Manufactured Table Study. Plaintiffs point out that this study was

necessary because at the time of baseline testing, Defendants had not produced any

tablets from one of the manufacturing sites (Jurong).476 Plaintiffs manufactured its

own tablets from the API from both Jurong and a different manufacturer (BI), to

tests for differences in degradation. It found none, countering any argument that the

pill testing was not representative. Any criticisms of the test relating to Emery’s

473 Id. 474 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 53. 475 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 268. 476 Id. 93 failure to use “proprietary protective coating or actual packaging”477 can be

advanced in cross examination.

8. Stress Testing. This challenge, like many of the foregoing, distills to the

design of the test (i.e., Emery exposed ranitidine to: “high levels of heat and

humidity,” employing “implausible conditions.”).478 Emery explained its use of

extreme conditions in defense of its simulations.479 That aside, again these criticisms

go to weight, not admissibility. They also “fit.”

Defendants’ final two challenges go to Reproducibility and the integrity of

Emery’s Delaware report.

j. Reproducibility

On reproducibility, Plaintiffs frame the formative issue this way: “The

question to be answered by this Court is not whether the data reported in Emery’s

MDL Report is reproducible, but whether the data reported in [Emery’s] Delaware

Report, the only proffered opinion here, is reliable, reproducible, and admissible.”480

Plaintiffs counter that this “entire argument hinges on the claim that the results

reported in the Delaware Report do not match the results reported in the MDL

477 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 55. 478 Id. at 53. 479 Id. 480 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 269. 94 Report.”481 Plaintiffs concede that the results from the two studies do not match due

to tabulation and sorting errors.482 But they argue that those errors do not impact the

reproducibility of the testing done by Emery in this case.483

Defendants emphasize that “[n]othing Plaintiffs did [in between the MDL

Report and the Delaware Report] adequately cured the methodological shortcomings

recognized by the MDL Court.”484 But as Plaintiffs emphasize, the only opinion

being proffered here is the Delaware Report. As a practical matter, Defendants are

inviting this Court, again, to defer to the MDL decision on reproducibility. This

Court declines to do so.

The ability to reproduce a test turns on the availability and integrity of the data

from the test to be reproduced. The Court has already plowed this ground. But we

re-visit for ease of reference.

Plaintiffs maintain that “all of the underlying data has been produced to

Defendants,” including “the corresponding test names, lot numbers, etc., in Excel

format.”485 Plaintiffs go further, adding that “all of the written validated protocol,

underlying raw and processed data from the conduct of the testing was provided to

481 Id. 482 Id. 483 Id. 484 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 55. 485 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 270 (emphasis in original). 95 Defendants in [the proper] format, with printed versions in the form of PDFs, and

also stored electronically in the [proper] system.”486 Plaintiffs add that, for each

experiment that was run, each of which was validated, the results of that validation

were produced,487 and that beyond the “standalone validations,” they produced each

analytical run including calibrations and quality control injections used to further

validate the process run, as well as lab notebooks, in which each test was

documented, maintained contemporaneously by the analyst conducting the

experiment and counter signed by “another researcher who validated the

experiment.”488

All this production, Plaintiffs argue, allows Defendants to “conduct their own

data analysis to come up with whatever statistical calculations they wish;”

something, Plaintiffs note more than once, Defendants did not do.489 Defendants

“have never run any of their own tests on the pill samples tested by Emery, despite

their ability to do so. . . to see if they could or could not reproduce Emery’s results.

They have never done any re-processing or re-integration of the raw data provided

by Emery to determine whether they could or could not reproduce Emery’s

486 Id. at 257, 259; see id. at 272–73. 487 Id. at 256. 488 Id. at 256–57. 489 Id. at 258. 96 results.”490 “With this information, Defendants are able to do their own analysis,

their own processing and integration, report their results, and do their own

calculations of means, minimum and maximum values, or any other statistical

measure they wish. They did no such thing.”491 Defendants resort to ipse dixit: the

production, characterized as they deem appropriate, makes reproduction impossible.

They never say they tried to reproduce Emery’s results. Instead, they cite to the

MDL’s Order.492

Defendants devote considerable space to the numerous failings and

inconsistencies they find in Emery’s MDL and Delaware Reports.493 They also

chastise Emery for its inability to reproduce its own results. This criticism might

carry more weight if Emery were somehow prohibited from updating the report, or

even more so if Emery had not explained to Defendants why the data was updated

in the first instance.494 Further, none of the changes cited by Defendants concerns

the baseline testing results.495 Also, some of the results of the changes made by Dr.

Cheu following his review and re-processing are “actually lower than those reported

490 Id. at 269. 491 Id. at 273. 492 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 56–58 (citing In re Zantac, 644 F.Supp.3d at 1130). 493 See id. at 57–63. 494 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 271–74. 495 Id. at 276. 97 in the MDL Report,” belying any suggestion of bias to increase NDMA levels.496

None of these challenges is flattering. But many of them involve clerical

errors;497 its resolution fitted for twelve people in the jury box. For that reason, the

Court will not exclude Emery’s opinion. The Court has already considered the

incomplete/inadequate production issue. It stands on that decision.

k. Reverse-engineering of the Emery Report

This challenge is hampered by the fact that some of the re-testing favored

Defendants. Similarly, as noted above, the results from one of the changes made by

Dr. Cheu, following his review and re-processing, are lower than those reported in

the MDL Report.498 That statistic also contradicts an effort to increase NDMA

levels. Some of Plaintiffs’ corrections skewed the testing against Plaintiffs.499 The

extended discussion of what Dr. Cheu did and why also militates against

Defendants’ notion of reverse-engineering.500

l. Transparency and Suggestion of “Lawyer-Driven” Changes

Plaintiffs detail the bases for their defense of transparency:

1. By reporting data and calculating the averages across each individual test,

496 Id. at 274–75. 497 Id. at 271; see Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 63 n.119 (stating chromatogram “mistakenly processed twice”). 498 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 274–76. 499 Id. at 276. 500 Id. at 271–73; see id. at 276. 98 rather than reporting data as averages of multiple tests of the same lot and then

calculating overall average, Emery was able to report results in a format that was

fully transparent and allowed the inclusion of all the information Defendants

complained about not having in the MDL.501

2. Plaintiffs included all baseline testing in the Delaware Report.502

3. Emery re-processed and re-integrated “all of the testing it had done so that

the results contained in the Delaware Report matched 100% with the underlying

MassHunter data, and chromatograms therefrom.”503

These changes were made for three reasons:

First, Defendants complained that they were not able to match up the

individual test data reported with individual chromatograms and underlying raw and

processed data.504 Defendants complain now that this change is evidence of an intent

to bias the results.505

Second, Defendants accused Plaintiffs of cherry-picking data they reported

because there were “many more tests in the native MassHunter data produced to

501 Id. at 277. 502 Id. 503 Id. at 278. 504 See id. at 277. 505 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 63 (citing Dr. Cheu’s testimony) (arguing that lawyers made the decision to change methods). Contra Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 278–79. 99 Defendants than contained in the MDL Report.”506

Third, Defendants complained in the MDL of problems matching test results

on the printed PDF chromatograms generated by their experts from MassHunter data

produced by Plaintiffs there.507

The re-processing and re-integration resulted in some “changes to reported

values but none made a “material difference to the overall values reported.”508

“None of the above are changes in methodology[;] they are changes in the detail and

manner in which the results were reported.”509 These changes, along with the

production made by Plaintiffs described above, overcome any suggestion that

Plaintiffs’ methodology was not transparent.

Defendants’ final challenge to the Emery study sounds in the unfortunate

allegation that changes in Emery’s method of presentation of chromatograms and

underlying data, raw and processed, were “lawyer driven.”510 In support of that

accusation, Defendants cite one question and its response:

Q: Okay. Well, then why did your methodology of averaging change?

A: This was a decision that was made I believe with the -

506 See Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 277. 507 Id. at 277–78. 508 Id. at 276–78. 509 Id. at 278. 510 Defs.’ Br. in Supp. of Brand Defs.’ & Patheon’s Mot. to Exclude Emery Pharma at 65. 100 what is - the MDL lawyers.511

Defendants celebrate this answer as “definitive proof that Emery lacked a pre-

set protocol.”512 But contrary testimony followed only pages away.513 Dr. Cheu’s

testimony makes clear that “the method of presentation of the averaging and selected

results in the MDL Report was a decision made ‘with. . . the MDL lawyers.’”514 But

the immediately following testimony “makes clear that the method of presentation

of the results in the Delaware Report was made by Emery.”515

The Court finds insufficient evidence that a lawyer-driven methodology

manipulated the Emery study and rejects that assertion. Those allegations comprise

only questions to be resolved by those in the jury box.

The Motion to exclude the Emery Pharma opinions is DENIED.

V. CONCLUSION

Although Daubert may have been intended to streamline expert practice under

Rule 702, this case, like many around the country, suggests that goal has proven

elusive. Differences in jurisprudence, interpretation of the law, and analyses may

confound simpler approaches to such motions.

511 Id. at 68. 512 Id. 513 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 279; Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. Ex. 173, at 160:7–161:11. 514 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 278–79. 515 Pls.’ Opp’n to Defs.’ Mot. to Exclude Gen. Causation Experts’ Op. at 279 (emphasis added). 101 In Delaware, our jurisprudence counsels that, subject to earnest deliberation,

trial courts entrust questions of science to the scientists. Here, opposing teams of

highly educated, skilled expert medical witnesses offer competing opinions.

Through well-trained counsel, their efforts only clarify the distinct opposition that

defines their respective positions. It would be improper to simply dismiss these

experts as “poseurs or witnesses for hire. They are serious scientists.”516 As

gatekeeper, the Court has found that each side has carried its required burden of

demonstrating the reliability of its proffered Rule 702 evidence. Any remaining

challenges will be made at trial via cross-examination and introduction of counter

evidence. Having considered the full record herein, the parties’ Daubert challenges

fail and their Motions to Exclude are DENIED.

IT IS SO ORDERED.

/s/ Vivian L. Medinilla Vivian L. Medinilla Judge cc: All Counsel of Record

516 In re Asbestos Litig., 911 A.2d at 1207.