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Currently, there is scientific debate regarding the carcinogenic potential of human exposure to nitrosamines in pharmaceuticals, and what nitrosamine concentrations constitute a virtually safe dose (e.g., one of no regulatory concern). Two major drugs, valsartan (used to treat hypertension), and ranitidine (used to treat indigestion, heartburn, and acid reflux) were voluntarily recalled from the market due to nitrosamine contamination in concentrations that were above Acceptable Daily Intakes (ADIs) set by regulatory agencies. Not surprisingly, personal injury litigation surrounding nitrosamine impurities in pharmaceuticals followed. Recently, two major cases involving valsartan and ranitidine were resolved by motions for summary judgment. Scientific analysis by our firm was cited in the valsartan decision.
Paustenbach and Associates were retained as the experts for Sandoz in the Valsartan litigation in Canada, where the judge’s decision was handed down on the matter in June of 2022. In this case, Plaintiffs alleged that exposure to N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) when taking contaminated valsartan increased the risk of developing cancer. It appears that our opinion letter was partially instrumental in informing the Judge on the scientific and risk assessment aspects of the matter. Specifically, the Judge stated that:
“Dr. Paustenbach, one of the Defendants’ toxicology experts, stated in his report, that estimating the quantitative risk to humans from animal data is problematic because the data is unreliable and because humans have DNA repair mechanisms that don’t exist in animals. He testified that the ADI is artificial, not based on a scientific methodology, and is not predicative of the human cancer risk ... As was noted by Dr. Paustenbach, the Defendants’ toxicology expert, every day through food and beverage consumption, humans are exposed to NDMA and NDEA far above the regulators’ A[D]I” (Judge’s Ruling in Palmer v. Teva Canada: pg. 15).
The ruling further agreed with our opinion that “Although the carcinogenicity of NDMA and NDEA in humans has been scientifically examined for decades, no scientific or regulatory body has definitively classified NDMA or NDEA as a carcinogen for human beings” (Judge’s Ruling in Palmer v. Teva Canada: pg. 13). Thus, when addressing Plaintiffs’ allegation that “exposure to NDMA or NDEA increases the risk of being diagnosed with cancer”, the Judge concluded that “… there is no basis in fact to come to that conclusion” (Judge’s Ruling in Palmer v. Teva Canada: pg. 14).
In December, 2022, a United States Judge dismissed a multidistrict litigation (MDL) case, which involved more than 2,450 plaintiffs filing lawsuits against manufacturers of ranitidine. Plaintiffs alleged that ranitidine caused cancer due to NDMA contamination in the ranitidine product itself, and due to endogenous formation of NDMA following ranitidine ingestion. In the 300+ page ruling, the Judge reported that:
“Here, there is no scientist outside this litigation who concluded ranitidine causes cancer, and the Plaintiffs’ scientists within this litigation systemically utilized unreliable methodologies with a lack of documentation on how experiments were conducted, a lack of substantiation for analytical leaps, a lack of statistically significant data, and a lack of internally consistent, objective, science-based standards for the evenhanded evaluation of data” (Judge’s Ruling in Zantac Products Liability Litigation: pg. 7).
The Judge concluded that since the plaintiffs did not have this evidence with which to establish general causation between ranitidine and cancer “… then there is no genuine dispute of material fact, and the defendant is entitled to judgment as a matter of law” (Judge’s Ruling in Zantac Products Liability Litigation: pg. 336).
Paustenbach and Associates scientists have over 40 years of experience in conducting pharmaceutical safety assessments and in evaluating the potential health risks of impurities in consumer products. We have conducted hundreds of risk assessments over the years. We have assisted several firms who have faced challenges involving nitrosamines (including NDMA, NDEA, and novel nitrosamines) in their product(s) as they deal with the press, regulatory agencies, and litigation.