The Lack of Present Injuries and Reliable Scientific Evidence Proves Fatal in North American Pharmaceutical Impurity Litigation

June 01, 2023

Written By Cheryl Woodin and Tom Feore

After reports were made regarding the presence of nitrosamines in certain pharmaceutical products in 2018 and 2019, and subsequent precautionary regulatory action was taken, an avalanche of litigation commenced in Canada and the United States regarding alleged failures by drug manufacturers, wholesalers, distributors and retailers in respect of a host of pharmaceutical products, including Valsartan, Ranitidine and others.

Nitrosamines are a ubiquitous class of chemical compound widely found in low levels in drinking water, vegetables, meats, cheeses, alcoholic beverages and other sources.

The plaintiffs in these various cases generally asserted that the presence of nitrosamines in pharmaceuticals either caused their cancer, or increased their risk of cancer.

In 2022, the Ontario Superior Court of Justice and the United States District Court Southern District of Florida each dismissed nitrosamine–related pharmaceutical class actions, regarding Valsartan and Ranitidine respectively. In May 2023, the British Columbia Supreme Court dismissed a similar nitrosamine-related pharmaceutical class action regarding Ranitidine.

The decisions of the Ontario Superior Court of Justice,  the United States District Court for the Southern District of Florida, and the British Columbia Supreme Court generally focused on two core factors:

1. the lack of a present injury; and
2. the lack of scientific evidence that the relevant (1) pharmaceutical products, and (2) nitrosamines, caused or increased the risk of cancer (i.e., the lack of general causation).

The Lack of a Present Injury

In Palmer v. Teva Canada Ltd. [Palmer], the lack of a materialized present injuries were a focus of Justice Perell’s decision to dismiss the certification motion, and the action as a whole.

In Palmer, the plaintiff’s case focused on the presence of nitrosamines in Valsartan, which the plaintiff alleged were carcinogenic. The plaintiff sought, on behalf of the proposed class, damages for their alleged increased their risk of developing cancer, and their mental distress associated with that allegedly increased risk, among other things.

Notably, the plaintiff did not seek damages for class members who had actually been diagnosed with a cancer, which Justice Perell found “baffling”.

The action was dismissed. Applying principles from the Supreme Court of Canada’s landmark decisions in 1688782 Ontario Inc. v. Maple Leaf Foods Inc. and Atlantic Lottery Corporation v. Babstock (where Bennett Jones acted for the appellant Atlantic Lottery Corporation), Justice Perell found that “negligence law does not recognize the risk of injury or harm or the increased risk of harm or injury as a compensable type of damages.”

In respect of the claims for damages arising out of distress over the alleged increased risk of cancer, Justice Perell found that such distress was no more than “present anxiety occasioned by the risk of future physical or psychological harm,” which was similarly non-compensable.

In Dussiaume v Sandoz Canada Inc. et al. [Dussiaume], Justice Wilkinson reached a similar conclusion in respect of similar claims. Despite the Plaintiff’s submissions to the contrary, she held that the Plaintiff had failed to allege any “manifested” health effects or conditions. Rather, she held, the Plaintiff’s claim was in truth about the risk of developing cancer. As such, it was not compensable for the same reasons identified in Palmer and consistent with the Supreme Court of Canada's analysis in Babstock. Justice Wilkinson also rejected the Plaintiff’s claim that consuming Ranitidine resulted in changes to his body’s cells and therefore resulted in a manifested injury; as she found it to be nothing more than “a potential future harm or increased risk of harm claim in different clothes.”

On the Plaintiff’s claims of psychiatric injury over the Health Canada notices and the alleged increased risk of cancer, Justice Wilkinson applied Palmer to conclude that anxiety occasioned by the risk of developing cancer is simply “a harm one step removed” from the non-compensable risk of physical injury, and was therefore similarly non-compensable.

In so doing, Justice Wilkinson also articulated a principled basis for the rule regarding psychiatric injury: citing the Supreme Court’s dictum in Saadati v Moorhead that different kinds of injury—namely, physical on the one hand and psychiatric on the other—should be afforded “identical treatment”, she determined that a claim for psychiatric injury based on an “apprehension of an abstraction (the increased risk of a diagnosis of cancer)” would “raise indeterminacy concerns, and would create a legal asymmetry between the availability of damages for a physical risk of harm and the availability of damages for mental harm flowing from a risk of harm.”

The Lack of Scientific Evidence (No General Causation)

Palmer v. Teva Canada Ltd.

The absence of some basis in fact that the relevant product and nitrosamines cause cancer (i.e., general causation) was another focus in Palmer.

In Palmer, Justice Perell scrutinized the epidemiological evidence and found that statistics from certain studies and experiments that suggest exposure to certain nitrosamines increases the experience of cancer “are a necessary but not a sufficient basis” to establish carcinogenicity to humans. Justice Perell held that “[i]t is an axiom of epidemiology that statistical association does not equate to proof of a causative relationship.”

Justice Perell also emphasized Health Canada’s study on the alleged theoretical increased risk from Valsartan, which found that “the theoretical additional cancer risk in a worst case scenario, range between one additional cancer case in every 11,600 persons to one additional cancer case in every 93,400 persons (i.e., a theoretical increased risk of cancer between 0.0086% and 0.0011%). As Health Canada had previously stated, and as Justice Perell emphasized, this theoretical increased risk must be considered in the context of the existing lifetime risk of a 50:50 chance of developing cancer. Justice Perell provided “further contextualization”, noting that the lifetime odds of dying in a motor vehicle accident are 0.91%.

Re: Zantac (Ranitidine) Products Liability Litigation

In Re: Zantac (Ranitidine) Products Liability Litigation [Zantac], Judge Rosenberg of the Southern District of Florida undertook a rigorous 314-page analysis of the plaintiffs’ expert evidence regarding Ranitidine in a Daubert motion.

Judge Rosenberg ultimately found that that “the Plaintiffs’ experts make analytical leaps that no scientist outside of this litigation has made. And the leaps go too far.”

Judge Rosenberg emphasized that there is “no widespread acceptance in the scientific community of an observable, statistically significant association between ranitidine and cancer”, and “no published study or governmental finding that agrees with the Plaintiffs’ experts—there is no published conclusion or finding, outside of this litigation, that concludes that ranitidine causes cancer of any kind.”

In evaluating the United States Food and Drug Administration’s (FDA's) testing results, which Judge Rosenberg found were “the only reliable testing”, she concluded “the average amount of [nitrosamine impurities] in ranitidine at roughly equivalent or slightly higher than the FDA’s daily limit which…equates to an infinitesimal unprovable risk of cancer.”

Dussiaume v Sandoz Canada Inc. et al.

In Dussiaume, in which Bennett Jones acted for Pharmascience Inc. and Laboratoire Riva Inc., the defendants brought a motion for summary judgment on the basis that there was no genuine issue for trial as to general causation, on the basis that the uncontroverted scientific evidence showed that there was no reliable association between Ranitidine and cancer, much less that Ranitidine could cause cancer. Justice Wilkinson agreed, and granted summary judgment in respect of all general and special damages claims on this basis.

Pointing to concessions by the Plaintiff’s experts in their reply reports that future studies would be needed in order to determine so much as a possible link between nitrosamines and/or Ranitidine on the one hand and cancer on the other, she noted that summary judgment cannot be defeated by vague references to what may be adduced in the future, and found that these were exactly what the Plaintiff had provided.

Ultimately, Justice Wilkinson held that the “uncontroverted evidence” was that “neither ranitidine nor NDMA [a nitrosamine impurity] are reliably associated with increased cancer risk”, and that there was an “absence of evidence that ranitidine or NDMA cause cancer in humans.” She concluded that “there is no scientific support for the conclusion that ranitidine at therapeutic doses gives rise to mutagenicity or is carcinogenic”.

Taken together, Palmer, Zantac and Dussiaume demonstrate courts' skeptical approach to risk of harm claims, particularly where the science does not demonstrate any such increased risk.

Looking Forward

While appeals and litigation are still pending, defendants should be encouraged by these courts' early focus on whether the claims being advanced are tenable at law and founded on credible existing science to support a claim for injury. The decisions all reinforce the proposition that class proceedings cannot be used to end-run these conditions precedent to an actionable wrong. 

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