On March 22, 2023, at the request of the U.S. Food and Drug Administration (“FDA”), Ascend Laboratories LLC. (“Ascend”) issued a voluntary nationwide recall of certain lots of Dabigatran Etexilate Capsules, a blood thinner medication, because of potential nitrosamine contamination.[i] Ascend is the most recent pharmaceutical manufacturer to issue a voluntary product recall because of the presence of nitrosamine impurities. Such impurities have also been identified in other recalled prescription and over-the-counter drugs, including those for treatment of elevated blood pressure, heartburn, acid reflux, and diabetes. Nitrosamine contamination is not limited to pharmaceuticals, as nitrosamine impurities have also been found in certain recalled personal care products, including (but not limited to) cosmetics, shampoos, conditioners, deodorants, tanning lotions, and hair dye.

What are Nitrosamines?

Nitrosamines are organic compounds that everyone is exposed to at some level and are common in water and foods, including cured and grilled meats, vegetables, and dairy products.[ii] Because nitrosamines come from chemical reactions, they can also form in drugs during the manufacturing, packaging, and storing stages. FDA has determined that some nitrosamines are human carcinogens and may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time.

In collaboration with its foreign regulatory counterparts, FDA has established recommended acceptable daily intake levels for different nitrosamines in drug products in a guidance document, Control of Nitrosamine Impurities in Human Drugs.[iii] According to FDA, a person “taking a drug that contains nitrosamines at, or below, the acceptable daily intake limits every day for 70 years is not expected to have an increased risk of cancer.”[iv] But “[i]f drugs contain levels of nitrosamines above the acceptable daily intake limits, FDA recommends these drugs be recalled by the manufacturer as appropriate.”[v] While the FDA guidance document recommends acceptable daily intake levels, it is likely to be hotly disputed whether there are actually any risks to health (much less causation) at any human-relevant exposure levels.

Other Voluntary Recalls and Legal Actions

Following FDA’s issuance of its guidance document in September 2020—which was finalized in February 2021—there have been numerous voluntary recalls of various pharmaceutical drugs because of potential nitrosamine contamination.[vi] Recalled products include valsartan, irbesartan, losartan, metformin, ranitidine, and nizatidine.

As expected, many of these product recalls spurred legal actions, the most prominent of which is likely the federal multi-district litigation over Zantac (ranitidine), In re: Zantac (Ranitidine) Products Liability Litigation. According to Bloomberg in September 2022, “[a] recent report from Morgan Stanley says trial judgments over nitrosamines against the makers of Zantac … could reach $45 billion alone.”[vii] In December 2022, however, the U.S. District Judge presiding over the federal litigation dismissed the nearly 50,000 cases pending in that consolidated action for failure to offer credible scientific evidence that the heartburn medication caused certain cancers.[viii] Other cases focused on additional cancers remain in state courts and those number in the tens of thousands.[ix]

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Nelson Mullins continues to closely monitor developments regarding FDA recalls and regulatory developments as well as the litigation risks they create.

[i] U.S. Food & Drug Admin., Ascend Laboratories LLC. Issues Voluntary Nationwide Recall of Dabigatran Etexilate Capsules, USP 75 mg and 150 mg, Due to the Detection of N-Nitroso-dabigatran (NDAB) Impurity (Mar. 23, 2023), https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/ascend-laboratories-llc-issues-voluntary-nationwide-recall-dabigatran-etexilate-capsules-usp-75-mg

[ii] U.S. Food & Drug Admin., What to Know and Do About Possible Nitrosamines in Your Medication (June 2020), https://www.fda.gov/consumers/consumer-updates/what-know-and-do-about-possible-nitrosamines-your-medication#:~:text=The%20FDA%20and%20the%20international%20scientific%20community%20do,health%20care%20professionals%20about%20alternative%20treatments%20if%20needed.

[iii] U.S. Food & Drug Admin., Control of Nitrosamine Impurities in Human Drugs (Feb. 2021), https://www.fda.gov/media/141720/download.

[iv] U.S. Food & Drug Admin., Information about Nitrosamine Impurities in Medications (Nov. 2021), https://www.fda.gov/drugs/drug-safety-and-availability/information-about-nitrosamine-impurities-medications#updates.

[v] Id.

[vi] U.S. Food & Drug Admin., Recalls, Market Withdrawals, & Safety Alerts (Mar. 2023), https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts.

[vii] Edney, A., A New Contaminant Found in Popular Drugs Could Cost Big Pharma Millions, Bloomberg (Sept. 1, 2022), https://www.bloomberg.com/news/articles/2022-09-01/drug-recalls-for-nitrosamines-could-cost-big-pharma-millions#xj4y7vzkg.

[viii] Frankel, A., Drugmakers’ huge win in consolidated Zantac case shows process can work for defendants, Reuters (Dec. 7, 2022), https://www.reuters.com/legal/litigation/drugmakers-huge-win-consolidated-zantac-case-shows-process-can-work-defendants-2022-12-07/.

[ix] Pierson, B., Judge weighs key evidence ahead of first Zantac cancer trial, Reuters (Feb. 16, 2023), https://www.reuters.com/legal/judge-weigh-key-evidence-ahead-first-zantac-cancer-trial-2023-02-16/.