In 2020, batches of metformin-containing medicines were recalled because they contained N-nitrosodimethylamine (NDMA), a probable human carcinogen, above the acceptable daily intake (AI) of 96 ng/day. Prior to the recalls, Official Medicines Control Laboratories (OMCLs) from the OMCL Network participated in an international collaboration of regulatory laboratories to analyse metformin active pharmaceutical ingredients (APIs) and finished dosage forms (FDFs) for this impurity.
Overall, 215 APIs and 875 FDFs were analysed between November 2019 and July 2020 by 10 regulatory laboratories using multiple procedures.
Regulatory agencies continue to collaborate extensively and work with marketing authorisation holders to understand the root causes of nitrosamine formation and agree on corrective actions to mitigate the presence of NDMA in future metformin batches.
A scientific article presenting an overview on the results obtained was published recently in The AAPS Journal and is available online
Keire, D.A., Bream, R., Wollein, U. et al. International Regulatory Collaboration on the Analysis of Nitrosamines in Metformin-Containing Medicines. AAPS J 24, 56 (2022).