The European Medicines Agency (EMA) has provided an update on its investigation into the findings that certain sartan products were contaminated with nitrosamine impurities.
It revealed that companies will have a two-year transition period to allow changes to be made to the manufacturing of products, during which temporary limits on the permissible levels will be applied. The agency expects companies to develop testing regimes able to detect trace amounts of the contaminants.
Once the transition period is over, the EMA stated that all companies will be required to demonstrate that their products can be produced without any trace of either N-nitrosodimethylamine (NDMA) and N‑nitrosodiethylamine (NDEA).
Cause of impurities
The release follows the US Food and Drug Administration (FDA)’s suggestion that the impurities had been created by the potential re-use of solvents.
Following its own investigation, the EMA stated: “It is now known that these impurities can form during the production of sartans that contain a specific ring structure known as a tetrazole ring under certain conditions and when certain solvents, reagents, and other raw materials are used.
The statement continued, “In addition, it is possible that impurities were present in some sartans because manufacturers had inadvertently used contaminated equipment or reagents in the manufacturing process.”
Though the EMA has drawn its conclusions as the cause of the impurities, the reaction to the discovery is not yet over; the agency has submitted its recommendations to the European Commission, which will make a legal decision on the matter.
The EMA noted it will also continue investigating the presence of NDMA and NDEA in medicines to determine what can be done to improve the way such processing errors are ‘identified and handled.’
It also named three other substances that will be investigated: N-nitrosoethylisopropylamine, N-nitrosodiisopropylamine, and N-nitroso-N-methylamino butyric acid.
A spokesperson for the EMA explained, "During the review of NDMA and NDEA in sartan medicines, EMA and national authorities also identified other nitrosamines, including N-nitrosoethylisopropylamine (EIPNA), N-nitrosodiisopropylamine (DIPNA) and N-nitroso-N-methylamino butyric acid (NMBA), that could potentially be formed during the synthesis of sartans with a tetrazole ring."
"We will look at all the available evidence about these additional nitrosamines to see how medicines in the EU might be affected. EMA will communicate further should it be necessary," the spokesperson continued.