11 of 22 pharma companies that Valisure tested had batches that exceeded the FDA daily acceptable limit for N-Nitrosodimethylamine (NDMA), a probable human carcinogen

NEW HAVEN, CT – MARCH 2, 2020, 6:45 AM – Valisure has tested and detected high levels of N-Nitrosodimethylamine (NDMA) in specific lots of the drug metformin, a prescription medication used to control high blood sugar in adults and adolescents with type 2 diabetes.

Valisure’s analysis of 22 companies selling metformin and a total of 38 batches revealed 16 batches and 11 companies where NDMA levels were detected above the 96 nanograms (ng) daily acceptable intake limit. Several batches contained over 10 times the daily acceptable intake limit and there was significant variability from batch to batch, even within a single company. These findings underscore the importance of batch-level chemical analysis and the necessity of effective quality surveillance of medications.

In a Citizen Petition filed with the Food and Drug Administration (FDA) on March 2, 2020, Valisure urged FDA to request recalls for the identified lots of metformin consistent with FDA’s mandate to ensure the safety of the drug supply in America. The carcinogenic nature of nitrosamines, and specifically NDMA, has been extensively studied by the scientific community since the 1960s. The World Health Organization (WHO) and the International Agency for Research on Cancer (IARC) have classified NDMA as a Group 2A compound thereby defining it as “probably carcinogenic to humans.” FDA currently recognizes the danger of this compound and, as a result, has set strict daily acceptable intake limits and advised companies to recall medications like valsartan, losartan, and ranitidine that did not meet this standard.

Links to Valisure’s FDA Citizen Petition, it’s attachments and Valisure’s detailed scientific findings are below:

Valisure’s FDA Citizen Petition on Metformin

Attachment A – Valisure’s Analytical Methods for Metformin Analysis via LC/HRMS

Attachment B – American College of Cardiology Resolution – Chemical Variability in Pharmaceutical Products

Valisure FDA Citizen Petition Comment Letter (May 31, 2020)

Official Regulatory Docket FDA-2020-P-0978: “Request that the FDA recall of identified batches of metformin”

Valisure was first alerted to this potential contamination in metformin after an individual client requested that Valisure test a sample of metformin medication.

“During testing of the medication sample of metformin, we used our standard testing process, which includes screening medications for the presence of the probable carcinogen N-Nitrosodimethylamine (NDMA), implicated in the global recalls of hypertension medications and most recently ranitidine. In this particular sample, we identified the presence of NDMA at higher than acceptable daily limits,” stated Kaury Kucera, PhD, Chief Scientific Officer of Valisure. “This finding prompted us to conduct a broader sweep of companies selling metformin. We found this was not an isolated incident and that there are many batches that contain unacceptable levels of NDMA. These findings underscore the importance of chemically validating all batches of medications for safety and quality.”

Valisure sent samples from a contaminated batch to be independently verified by Emery Pharma, an FDA registered/inspected, cGMP/GLP compliant analytical laboratory located in Alameda, California. Emery’s results confirmed Valisure’s findings of many times the FDA acceptable daily intake limit of NDMA for the re-tested batch.

Metformin is an oral diabetes medicine that helps control blood sugar levels in patients with type 2 diabetes. More than 30 million people in the United States have diabetes, of which 90 to 95% are type 2. Metformin is the fourth-most prescribed drug in the U.S. with approximately 80 million prescriptions written in 2019.

“The presence of this carcinogen in metformin where multiple tablets can be taken daily and often for a lifetime diabetic condition, makes this finding particularly concerning,” said Deanna Akinbajo, PharmD, MPH, Chief Pharmacist of Valisure. “Furthermore, the increased prevalence of diabetes in adolescents and young adults strongly underscores the need for quick action to protect patients.”

“The contamination in these batches of metformin appears to be similar to the issues that continue to plague blood pressure medications like valsartan and losartan. Valisure urges FDA and industry to take swift and broad action to clean up the U.S. supply of metformin, a drug that tens of millions of Americans rely on. We must strive to avoid a repeat of over year-long rolling recalls that patients and practitioners still endure with blood pressure medications,” stated David Light, Founder and CEO of Valisure. “Valisure’s results indicate that contaminated batches of drugs are scattered and intermixed with clean ones throughout the American pharmaceutical supply chain. This strongly suggests that neither the limited testing FDA is able to conduct nor the pharmaceutical companies’ self-reporting of analytical results is sufficient to protect American consumers from potentially dangerous contamination in the U.S. drug supply. Independent, third-party analysis of medication taken direct from pharmacy supply is needed more than ever.”

Summary comparison of batch-level data from various companies selling metformin as analyzed and/or reported by FDA, Health Canada and Valisure:

Media Coverage Below

Bloomberg:  Carcinogen Found by Pharmacy in Popular U.S. Diabetes Drug

Reuters: Online pharmacy Valisure says tests show carcinogen in diabetes drug metformin

The People’s Pharmacy: Several Metformin Diabetes Drugs Contaminated with Nitrosamine

FiercePharma:  Testing lab challenges FDA findings that carcinogens in metformin do not exceed acceptable levels

STAT News: FDA petitioned to recall batches of metformin diabetes pill over a possible carcinogen

NYTimes: Online Pharmacy Valisure Says Tests Show Carcinogen in Diabetes Drug Metformin

Becker’s Hospital Review:  Carcinogen detected in popular diabetes drug; FDA recall sought 

Business Insider:  Online pharmacy Valisure says tests show carcinogen in diabetes drug metformin

Physician’s Weekly:  Online pharmacy Valisure says tests show carcinogen in diabetes drug metformin

MedPage Today:  More Carcinogen-Tainted Drugs

NASDAQ/The Motley Fool: Valisure Challenges FDA’s Claims on Metformin’s Safety Carcinogen found by pharmacy in popular U.S. diabetes drug

FDA News: Online Pharmacy Urges FDA to Pull Metformin Products With High NDMA Levels

The Straits Times: Carcinogen found by US pharmacy in diabetes drug metformin

India Times: Online pharmacy Valisure says tests show carcinogen in diabetes drug metformin

Pharmacy Times:  High Levels of Carcinogen NDMA Found in Common Diabetes Medication

Photo credit:  Jake Chiles