Nitrosamine Impurities Trace in Metformin

GMP Practice Considerations for Responding to COVID 19
Good Manufacturing Practice (GMP) Considerations for Responding to COVID-19 Infection in Employees in Drug & Biological Products Manufacturing
July 3, 2020
Nitrosamine impurities -A regulatory perspective
Nitrosamine Impurity: A Regulatory Perspective
July 6, 2020
Nitrosamine impurities traces in Metformin
Please share the blog


Metformin is a prescription drug used to control high blood sugar in patients with type 2 diabetes. The Regulatory agency announced that traces of Nitrosamine present in generic drug substances and drug products, further FDA and EMA investigation also led to the detection of these Nitrosamine impurities in low levels of NDMA impurity in Metformin.

Recent investigation:

FDA has been investigating the presence of nitrosamines in drug products and in late 2019, become aware of NDMA in some Metformin products in other countries. The regulatory agency started testing to determine whether the Metformin in the U.S. supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types. In February 2020, they had identified very low levels of NDMA in some samples, but at that time, no FDA-tested sample of Metformin exceeded the acceptable intake limit for NDMA. The FDA has maintained that it would continue with ongoing testing of Metformin and other medications, and if any levels of NDMA or other impurities were identified, swift action would be taken. Recently FDA became aware of reports of higher levels of NDMA in certain extended-release (ER) formulations of  Metformin.

In addition, EMA and national authorities are also assessing the impact of recent tests that found NDMA in some EU batches of Metformin medicines, used for diabetes. Further results from tests on Metformin in the EU are being awaited. In line with previous advice, patients should continue taking their Metformin medicines as usual. The risk of not having adequate diabetes treatment far outweighs possible risks from low levels of nitrosamines.

As Metformin is considered a critical medicine, EMA and national authorities are cooperating closely to avoid possible shortages so patients can continue to get the treatments they need

Lab testing for the analysis of NDMA in metformin

FDA continues to investigate the presence of the N-Nitrosodimethylamine (NDMA) impurity in Metformin approved for sale in the U.S. Metformin is a prescription drug used to control high blood sugar in patients with type 2 diabetes. FDA testing has found NDMA in certain lots of extended-release (ER) Metformin and is recommending companies recall lots with levels of NDMA above the acceptable intake limit of 96 nanograms per day. FDA is also collaborating with international regulators to share testing results for Metformin. For reference, consuming up to the acceptable daily intake limit, 0.096 micrograms (96 nanograms), of NDMA per day is considered reasonably safe for human ingestion based on lifetime exposure. NDMA may increase the risk of cancer if people are exposed to it above the acceptable level and over a long period 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


 The FDA, EMA, and other regulatory authorities are working closely with international drug regulatory agencies and have been testing drug products for NDMA and are collaborating to investigate the sources of these Nitrosamine impurities in Metformin, because of its extreme toxicity regulatory authorities put forth the expectation of appropriate risk assessment and control strategy.

Read our Blogs

Forced Degradation Studies for Drug Substances & Drug Products- Scientific Considerations

Forced degradation studies for Drug Substances and Drug Products- A Regulatory Considerations

Thermogravimetric Analysis in Pharmaceuticals

Dexamethasone, Potential treatment on Covid-19


  • FDA alerts on nitrosamine impurity findings in metformin, available at
  • European medicines agency, available at
  • Laboratory analysis of metformin products, available at

To know more about Impurities and Pharmaceutical Drug substance read our blogs or to buy them visit Our website


  1. […] Nitrosamine impurities trace in Metformin […]

  2. […] Nitrosamine Impurity traces in Metformin […]

Leave a Reply

Your email address will not be published. Required fields are marked *