In re Zantac (Ranitidine) Prods. Liab. Litig.

Decision Date06 December 2022
Docket NumberMDL 2924,20-MD-2924
PartiesIN RE: ZANTAC (RANITIDINE) PRODUCTS LIABILITY LITIGATION
CourtUnited States District Courts. 11th Circuit. United States District Courts. 11th Circuit. Southern District of Florida

IN RE: ZANTAC (RANITIDINE) PRODUCTS LIABILITY LITIGATION

MDL No. 2924

No. 20-MD-2924

United States District Court, S.D. Florida

December 6, 2022


BRUCE E. REINHART MAGISTRATE JUDGE

OMNIBUS ORDER ON ALL PENDING DAUBERT MOTIONS AND DEFENDANTS' SUMMARY JUDGMENT MOTION

ROBIN L. ROSENBERG UNITED STATES DISTRICT JUDGE

Table of Contents

I. Introduction.............................................................................................................................3

II. Factual and Procedural Background........................................................................................7

A. Factual Background.............................................................................................................8

B. Procedural Background......................................................................................................10

1. Creation of this MDL.....................................................................................................10

2. Plaintiffs' Master Complaints........................................................................................11

3. Discovery.......................................................................................................................14

4. Designated Cancers........................................................................................................14

C. Present Procedural Posture................................................................................................15

1. Expert Reports................................................................................................................15

2. Daubert and Summary Judgment Briefing....................................................................18

III. Applicable Legal Standards...................................................................................................20

A. Admissibility of Expert Opinions......................................................................................20

1. Qualification...................................................................................................................21

2. Reliability.......................................................................................................................21

3. Helpfulness.....................................................................................................................23

B. General Causation..............................................................................................................24

1. Definition of General Causation....................................................................................24

2. General Causation Inquiry in this MDL.........................................................................25

IV. Framing the General Causation Question in this MDL.........................................................29

V. Amount of NDMA in Ranitidine...........................................................................................35

A. Plaintiffs' Internal Testing for NDMA in Ranitidine...........................................................39

1. Dr. Najafi and Emery Pharma's Testing........................................................................39

1

2. Experts Relying on Dr. Najafi and Emery Pharma's Testing......................................121

3. Final Ruling on Plaintiffs' Internal Testing.................................................................124

B. External Testing for Endogenous Formation of NDMA.................................................124

1. In Vivo Studies.............................................................................................................126

2. In Vitro Studies.............................................................................................................145

C. Conclusion on the Amount of NDMA in Ranitidine.......................................................158

VI. Primary Evidence of General Causation.............................................................................159

A. Epidemiology...................................................................................................................161

1. Summary of Epidemiological Concepts.......................................................................161

2. Summary of Parties' Arguments..................................................................................168

3. Defendants' Generalized Challenges to Plaintiffs' Epidemiology Experts.................169

4. Defendants' Specific Challenges to Plaintiffs' Epidemiology Experts.......................227

5. Final Ruling on Epidemiology Motion........................................................................298

B. Dose-Response Relationship...........................................................................................299

1. Dr. Salmon's Dose-Response Relationship and Threshold Dose Opinions.................302

2. Remaining Experts' Dose-Response Relationship Opinions.......................................309

3. Drs. Panigrahy, Michaels, McTiernan, and Moorman's Threshold Dose Opinions .... 313

C. Background Risk..............................................................................................................319

D. Conclusion on Plaintiffs' Primary Evidence....................................................................321

VII. Secondary Evidence of General Causation.........................................................................322

A. Animal Studies.................................................................................................................322

1. Species and Dose Extrapolation...................................................................................323

2. Cancer Diagnosis Extrapolation...................................................................................330

B. FDA's Regulatory Risk Assessments..............................................................................333

1. Parties' Arguments.......................................................................................................333

2. Analysis........................................................................................................................334

C. Conclusion on Plaintiffs' Secondary Evidence and Overall Daubert Conclusions.........336

VIII. Summary Judgment...........................................................................................................336

Appendix.....................................................................................................................................338

2

I. Introduction

This multidistrict litigation (“MDL”) is about Zantac heartburn medication or, more particularly, the molecule marketed under the label name of Zantac: ranitidine. Ranitidine is no longer sold in the United States and many other parts of the world because, in the spring of 2020, the U.S. Food and Drug Administration requested that the manufacturers of ranitidine voluntarily recall their products and cease all future sales. All manufacturers complied. The voluntary recall of ranitidine is a logical starting point for the facts underlying this MDL, but it is not the best starting point.

The best starting point involves a private company known as Valisure. Valisure theorized that ranitidine has the potential to degrade into a carcinogen known as NDMA. To evaluate this theory, Valisure tested batches of ranitidine in various conditions and found NDMA—lots of it. To put the Valisure test results into proper context, the FDA's self-determined daily limit for NDMA in a drug is 96 nanograms, or 96 ng. Valisure's tests found NDMA in ranitidine in excess of 3,000,000 ng.

To achieve a test result of 3,000,000 ng, however, Valisure had to heat the ranitidine to a temperature well above the 98 degrees Fahrenheit found in the human body; Valisure used a temperature of 266 degrees Fahrenheit. When Valisure tested ranitidine with a temperature of 98 degrees Fahrenheit, Valisure detected no NDMA.

Valisure's testing, however, extended beyond just temperature-based tests. Using the human body's base temperature, Valisure tested ranitidine's reaction with salt in an artificial stomach. Once ranitidine was mixed with salt, Valisure detected NDMA in excess of 300,000 ng. The amount of salt Valisure used, however, is worth noting. According to a Plaintiffs' expert in this MDL, the amount of salt Valisure used to generate 300,000 ng of NDMA was so great that it

3

was close to the level where, upon consumption, the salt intake would cause death. When Valisure tested ranitidine with salt concentrations more closely approximating what a human could safely ingest, Valisure detected no NDMA.

Valisure presented its findings to the FDA. The FDA did not immediately act on Valisure's information, however, for at least two reasons. First, the FDA concluded that the laboratory equipment that Valisure used to test for NDMA actually created NDMA. In other words, Valisure's laboratory equipment created the very substance for which it was testing. Second, the FDA wanted to conduct its own tests using laboratory equipment that did not create NDMA. Using its own laboratory equipment, the FDA tested ranitidine pills from several different manufacturers. Some of the ranitidine pills tested showed no NDMA or almost no NDMA. Others showed NDMA, but the NDMA was below the FDA's limit of 96 ng. Some ranitidine pills did show NDMA above 96 ng, but even the highest-tested pill showed NDMA at a tiny fraction of the level reported by Valisure.

Why then did the FDA initiate a voluntary recall of ranitidine? Although the FDA's tests revealed NDMA levels far below Valisure's, and although many of the FDA's tests showed NDMA levels that were...

To continue reading

Request your trial

VLEX uses login cookies to provide you with a better browsing experience. If you click on 'Accept' or continue browsing this site we consider that you accept our cookie policy. ACCEPT