Statement from Janet Woodcock, M.D., director of FDA's Center for Drug Evaluation and Research, on impurities found in diabetes drugs outside the U.S.

SILVER SPRING, Md., Dec. 5, 2019 /PRNewswire/ -- The U.S. Food and Drug Administration has been investigating the presence of genotoxic impurities, called nitrosamines, in some types of drugs. Over the past year and a half, several drug products including angiotensin II receptor blockers (ARBs) and ranitidine, commonly known as Zantac, have been found to contain small amounts of nitrosamines such as N-Nitrosodimethylamine (NDMA). During this time, there has been an ongoing investigation into the presence of nitrosamines in other drug products. This effort is focused on ensuring the drugs used by Americans continue to meet strict quality standards.

The FDA is aware that some metformin diabetes medicines in other countries were reported to have low levels of NDMA. Based on the information we have available, the levels of NDMA seen outside the U.S. are within the range that is naturally occurring in some foods and in water. While we are aware that some regulatory agencies outside the U.S. may be recalling some metformin drugs, there are no metformin recalls affecting the U.S. market at this time. The FDA is investigating whether metformin in the U.S. market contains NDMA, and whether it is above the acceptable daily intake limit of 96 nanograms. The agency will also work with companies to test samples of metformin sold in the U.S. and will recommend recalls as appropriate if high levels of NDMA are found. If as part of our investigation, metformin drugs are recalled, the FDA will provide timely updates to patients and health care professionals.

Metformin is a prescription drug used to control high blood sugar in patients with type 2 diabetes. Patients should continue taking metformin to keep their diabetes under control. It could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their health care professional. The FDA recommends prescribers continue to use metformin when clinically appropriate, as the FDA investigation is still ongoing, and there are no alternative medications that treat this condition in the same way.

NDMA is a common contaminant found in water and foods including cured and grilled meats, dairy products and vegetables. Everyone is exposed to some level of NDMA. The FDA and the international scientific community do not expect it to cause harm when ingested at low levels. The acceptable daily intake limit for NDMA in the U.S. is 96 nanograms. Genotoxic substances such as NDMA may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time, but a person taking a drug that contains NDMA at-or-below the acceptable daily intake limit every day for 70 years is not expected to have an increased risk of cancer.

Today, we have better testing methods than ever before, and we know what to look for in products' chemical structure and manufacturing processes that may increase the risk of forming low levels of nitrosamines. Improved technology enables us to detect even trace amounts of impurities in drug products and may be the reason why more products have been found to have low levels of NDMA. The agency has strict standards for safety, effectiveness and quality, and our staff makes every effort to help keep the U.S. drug supply as safe as possible. We also work closely with international drug regulatory agencies so that we leverage resources and testing done outside the U.S. which can help inform testing of the U.S. drug supply. As our investigations and testing continues, along with the investigations done by other drug regulatory agencies, we may find low levels of nitrosamines in additional drugs.

The FDA will continue to investigate the source of these impurities, but it is important to note that there are multiple reasons why NDMA can be present in drugs. Previously, we found the source of NDMA can be related to the drug's manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed. The FDA continues to test and research possible sources for the several drugs found to contain NDMA.

We are taking a systematic approach to identify medicines with nitrosamines above acceptable daily intake limits and remove them from the market. For example, yesterday we announced expanded testing requirements for ranitidine manufacturers to help give consumers confidence that the drugs on the market do not have NDMA above the acceptable daily intake limit.

Our investigations, including our current investigation of metformin, take into account the medical necessity of the drug, how many Americans may take it, and whether there may be alternative treatments available. The American public can expect that we will act quickly to address any issue as soon as we find out about it.

These investigations take time. We understand that these issues affect patients' health and well-being in many ways, and the FDA's goal is to provide patients and health care providers as much clarity and as many answers as possible to inform their health care decisions. The FDA will communicate any information we have scientifically confirmed to ensure the public knows as much as possible as soon as possible.

Protecting patients is the FDA's highest priority, and Americans can be confident in the quality of the products the agency approves. We are patients too, and we're committed to maintaining our high standards for quality, safety and efficacy for all drugs we, our families, friends, colleagues and millions of fellow Americans rely on for their health.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Media Inquiries: Jeremy Kahn, 301-796-8671, jeremy.kahn@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA

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SOURCE U.S. Food and Drug Administration