Nitrosodimethylamine impurities in metformin drug products: Physician insight

Abstract

Metformin is a high-dose antidiabetic drug and most widely used first-line therapeutic agent for the management of type 2 diabetes mellitus (T2DM). Medicines regulatory agencies discovered contamination of genotoxic nitrosamine impurity in certain medications containing angiotensin receptor blocking (ARB) agents. This resulted in screening for nitrosamine impurities in a number of probable drug products. In November 2019, the Singapore government withdrew metformin drug products, due to the contamination of nitrosamine impurity, called nitrosodimethylamine (NDMA). The regulatory agencies from different geographies started investigation and subsequently, many products withdrew from the international market due to the presence of an unacceptable limit of NDMA in metformin tablets. Both pharmaceutical companies and regulatory agencies responded to mitigate this emerging issue. USV Private Limited (USV) has adopted a proactive quality risk management program to investigate the presence of genotoxic impurities in metformin products. The presence of NDMA impurities were tested in 425 batches of drug substances and drug products. Threshold toxicological concern (TTC) of all the batches was found to be ≤30 ng/day, when compared to the regulatory limit of 96 ng/day. Hence, USV metformin products are safe and can be continuously prescribed for the management of T2DM.

Keywords

• genotoxic
• impurity
• metformin
• nitrosamine
• regulatory
• usv