This year was a year where the word “safety” was particularly highlighted in the healthcare industry. The N-Nitrosodimethylamine (NDMA), a potentially carcinogenic substance, which caused a ruckus after being detected in valsartan-based antihypertensive treatment last year, was further extended to ranitidine and nizatidine. Earlier this month, the medical community was startled when the carcinogenic substance was found in some metformin products, which is the most widely used diabetes treatment in Korea. Also, the importance of drug safety was further highlighted through Allergan's breast implant safety issue and Kolon Life Science's Invossa incident. Along with safety issues, Korea Biomedical Review looked back on major issues that have affected the medical industry this year. - Ed
The N-nitrosodimethylamine (NDMA) crisis, which became a social problem last year, spread even further this year. Following the discovery of a cancer-causing substance in valsartan-based antihypertensive treatment previous year, the carcinogenic substance was additionally found in ranitidine and nizatidine, and more recently, metformin, an antidiabetic drug.
After collecting and testing ranitidine-containing products in September, the Ministry of Food and Drug Safety (MFDS) said it found seven raw materials that exceeded the NDMA’s provisional management criteria and banned the sales of 269 medicines using the raw material
The announcement came after the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) announced that NDMA was detected in Zantac, a representative ranitidine product.
As a result, the ranitidine market of 300 billion won ($258.1 million) disappeared into thin air as the products were withdrawn from the market.
However, the NDMA crisis didn't stop there. According to the ministry’s investigation, some of the nizatidine products with similar molecular structures also had NDMA, forcing the ministry to revoke the manufacturing and selling license of 13 items.
Besides, earlier this month, concerns about NDMA detection were raised in metformin, which is recommended as the first-line treatment of diabetes by various international drug regulators, including the FDA. As metformin is the standard therapy recommended as the first-line treatment for treating type 2 diabetes in Korea, the repercussion of the findings is expected to be huge.
The FDA and EMA are currently conducting NDMA tests on commercially available metformin products and will recall any of them that exceed their standards.
So far, Poland and Singapore have completed their NDMA testing on metformin. In Poland, a small amount of NDMA was found after the investigation, but no products exceeded the standard. In Singapore, NDMA was detected in more than three versions out of the 46 metformin-containing preparations, and a recall was initiated for those products.
As concerns about NDMA detection in metformin spread, the academic community urged the government to take countermeasures.
The Korean Diabetes Association (KDA) warned the government, noting that there are 640 metformin-containing drugs in Korea, and it is estimated that 2.4 million people, or 80 percent of diabetics, take the medicine.
“In the case of hypertension drugs or antacids, a variety of alternative drugs were possible, but metformin has no alternative drugs,” the association said. “This is not going to be solved by pharmaceutical companies' autonomous check of their products.”
In the U.S., Europe, and Japan, authorities are conducting their own investigations. At the same time, the FDA has posted a list of safe drugs on its website in real-time, the association added.
The KDA stressed that Korea should also address the public's concerns through direct investigations by the MFDS.
As the NDMA detection crisis continues, the ministry announced measures to manage impure pharmaceutical ingredients.
According to the new regulation, raw material companies and drug manufacturers should inspect all products for possible impurities such as NDMA and report them by next May. Those which produce drugs highly likely to contain impure substances should submit their test results by May 2021.
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