In October 2019, the director of the FDA’s Center for Drug Evaluation and Research, Dr. Janet Woodcock, testified before Congress that the United States “has become a world leader in drug discovery and development, but is no longer in the forefront of drug manufacturing.” According to Woodcock’s testimony, 72% of manufacturing for active pharmaceutical ingredients (APIs), which are considered the basic building blocks of medications, now takes place outside the U.S. Furthermore, the number of facilities making APIs in China has more than doubled since 2010. More and more, active pharmaceutical ingredients are being manufactured overseas in countries like China and India, where the health and safety standards aren’t as stringent as those in the U.S. Not only does this create “vulnerabilities in the U.S. supply chain,” Woodcock warned, it also increases the risk of problems caused by substandard or dangerous pharmaceuticals or pharmaceutical ingredients.
In 2018, the FDA recalled several medications containing the ingredient valsartan supplied by Zhejiang Huahai Pharmaceuticals (ZHP) of China and other overseas facilities. Valsartan is an angiotensin II receptor blocker (ARB) used to treat high blood pressure and heart failure and it was discovered that generic valsartan manufactured by ZHP and sold worldwide was contaminated with a cancer-causing substance called N-nitrosodimethylamine (NDMA). According to the FDA, “The presence of NDMA was unexpected and is thought to be related to changes in the way the active substance was manufactured.” After pharmaceutical companies began outsourcing the valsartan manufacturing process to facilities in China and India in order to reduce their costs, changes were made to the way valsartan was produced. As a result of these changes, NDMA reportedly occurred as a byproduct of the manufacturing process.
“We have carefully assessed the valsartan-containing medications sold in the United States, and we’ve found that the valsartan sold by these specific companies does not meet our safety standards,” said Janet Woodcock in announcing the recall of contaminated valsartan medications manufactured in China and India. “This is why we’ve asked these companies to take immediate action to protect patients.”
On the heels of the valsartan recalls, losartan, irbesartan and other popular ARB medications were recalled over similar concerns about a potential contamination with NDMA and other carcinogenic chemicals. The NDMA found in valsartan, losartan, irbesartan and other widely used pharmaceutical drugs has been classified as a probable human carcinogen, meaning exposure to the chemical could cause cancer in humans. Exposure to NDMA has been shown to put users at risk for a range of cancers, possibly including non-Hodgkin’s lymphoma, prostate cancer, leukemia, pancreatic cancer, multiple myeloma, stomach cancer, intestinal cancer or colon cancer.
The valsartan, losartan and irbesartan recalls were nowhere near the first time contaminants in pharmaceutical drugs manufactured overseas have exposed consumers to a potential risk of serious or life-threatening illness. In 2007 and 2008, nearly 250 people died as a result of contaminated heparin, a widely used blood thinner medication marketed by Baxter International Inc. An investigation by the U.S. Centers for Disease Control and Prevention (CDC) determined that certain batches of the drug manufactured in China had been contaminated by a man-made chemical called oversulfated chondroitin sulfate (OSCS), which caused some users to suffer complications like difficulty breathing, excessive sweating, decreased blood pressure, nausea or vomiting, life-threatening shock or death.
Since 2010, federal regulators have discovered similar problems affecting batches of muscle relaxers, thyroid medications and antibiotics used to treat tuberculosis, sexually transmitted diseases and other bacterial infections. In 2016, an explosion at a factory in China resulted in a global shortage of an antibiotic called piperacillin, due to the fact that the factory was the medication’s only source of production. In light of these major issues, experts have warned that being dependent on overseas manufacturers to produce the ingredients needed for life-saving medications sold in the United States needlessly puts American lives at risk. Unfortunately, without intervention, the FDA expects the pharmaceutical industry to continue to rely on poorly regulated facilities in China and India for the production of these much-needed pharmaceutical ingredients.