A second class of drugs was found to be contaminated with a known carcinogen, raising concern that the FDA is not adequately monitoring existing drugs on the market.

Drug regulators in both Europe and the United States are concerned about the safety of Zantac, a commonly used medication taken by millions of people for heartburn relief, because it might be laced with carcinogens.

News of Zantac’s possible contamination came last Friday when Reuters reported that Zantac, also known as ranitidine, was found to contain traces of “probable cancer-causing impurities in some versions of the medicine.”

The U.S. Food and Drug Administration (FDA) reported finding the impurity N-nitrosodimethylamine (NDMA), and both the FDA and Europe’s regulatory body, the European Medicines Agency, will take a much closer look at Zantac’s safety.

NDMA is an odorless, tasteless yellow liquid known to cause cancer in animals and classified as a probable carcinogen for humans. In particular, NDMA is toxic to the liver.

Impurities Found in Zantac

According to the Reuters report, the Zantac discovery came from online pharmacy Valisure which tests the medication it sells, and when test results showed the presence of the impurities in both branded Zantac (from maker Sanofi SA) and generic versions of ranitidine, Valisure alerted FDA regulators.

Neither Valisure nor the FDA is releasing information regarding the tests. They have not yet revealed which versions of the drug were found to have impurities, nor have they revealed the amounts of NDMA found. The FDA did note that differing amounts of NDMA were found in the different versions of ranitidine.

The problem with NDMA is not a new one. Last year, the same impurities were found in drugs called Angiotensin II Receptor Blockers or ARBs, used to treat blood pressure and heart failure. FDA regulators have been recalling those drugs since 2018. Valsartan, the generic version of Diovan (Novartis AG), has been recalled. Novartis Sandoz, as well as other companies like Mylan NV and Teva Pharmaceuticals, have recalled the drugs because they contained probable carcinogens.

NDMA can be manufactured during certain industrial processes where pesticides and dyes are made, so why is it showing up in drugs? The FDA reported in 2018 that the three companies mentioned above all bought the active pharmaceutical ingredient (API) for their valsartan formulations from China, specifically one of the biggest generic drugmakers, Zhejiang Huahai Pharmaceuticals.

How Consumers Are Affected

Bloomberg reports that the recall was expanded 51 times since the initial Zheijiang discovery. ARB drugs irbesartan and losartan were added to the list; 10 companies make those and sell them to millions of people in 30 countries around the world. Just last month, the FDA expanded its NDMA investigation beyond the class of ARB drugs to look at other drugs.

How are consumers affected? The FDA has estimated that people who took high daily doses of valsartan for four or more years are at greatest risk and an additional one in 8,000 could get cancer. European regulators say there is a higher risk, estimating one in every 3,390 people could get cancer.

How does something like this happen, particularly when the FDA’s rigorous new drug approval process is in place to prevent instances exactly like this? The answer lies in generic drugs. When a company invents a new drug, that company painstakingly goes through the years-long process of proving drug efficacy through human clinical trials.

Generic manufacturers then ride those coattails, only having to show that the patient will absorb their drug at the same rate as the name-brand medication. The generic drugs receive much less scrutiny, and 90% of all medications that Americans take are generic because they are cheaper.

US Pharmaceuticals Not Required to Label Drug Sourcing

To make matters worse, the large majority (80%) of APIs are made in factories in China and India. U.S. pharmaceutical companies are not obligated to let American consumers know their drugs are being sourced from foreign countries.

The FDA does a poor job of checking these drugs. In fact, less than 1% of drugs are tested for impurities before they come into the U.S. Inspection of overseas factories by the FDA is in sharp decline. Despite opening three offices in China over a decade ago and vowing increased monitoring, only the Beijing office is still open.

Meanwhile, the FDA says it, along with other world regulators, is “considering requiring new testing during the manufacturing process to reduce contamination of drugs.” According to Reuters, spokesperson Janet Woodcock, the director of the FDA’s Center for Drug Evaluation and Research, said that the FDA is simply going to have to be more vigilant: “I think you’ll see tests added at the appropriate point during the manufacturing.”