What are Nitrosamines?

Nitrosamines are a group of chemical compounds that are formed when a nitrosating agent reacts with an amine. Nitrosating agents are chemicals that contain nitrogen and oxygen in a specific arrangement. Amines are chemicals that contain nitrogen and hydrogen.

Nitrosamines are classified as probable human carcinogens.

To date there are seven nitrosamine impurities that have been identified in pharmaceuticals:

• N-nitrosodimethylamine (NDMA)
• N-nitrosodiethylamine (NDEA)
• N-nitroso-N-methyl-4-aminobutanoic acid (NMBA)
• N-nitrosoisopropylethylamine (NIPEA)
• N-nitrosodiisopropylamine (NDIPA)
• N-nitrosodibutylamine (NDBA)
• N-nitrosomethylphenylamine (NMPA)

Nitrosamines can be found in the starting materials, be formed during the manufacturing, or packing of pharmaceuticals, or be formed some time after the drug is released into the market.

The risk of nitrosamine formation is higher in certain types of drugs, such as blood pressure medications, heartburn medications, and diabetes medications.

Where can I read about Nitrosamine Impurities?

There is a lot of information on the internet about Nitrosamine impurities

FDA – Information about Nitrosamine Impurities in Medications | FDA

WHO – Information Note Nitrosamine impurities (who.int)

TGA – Nitrosamine impurities in medicines | Therapeutic Goods Administration (TGA)

Medsafe – Medsafe policy for nitrosamine impurities in medicines – information for sponsors

EMA – Nitrosamine impurities | European Medicines Agency (europa.eu)

What do sponsors need to do to about Nitrosamines? 

You need to assess the potential for nitrosamines in the product, as well as the potential for the product to be contaminated with nitrosamines.  The actions you need to take depend on where you are manufacturing and selling the product.

For products manufactured in, or sold into Australia refer to the TGA for more information:  Therapeutic Goods Administration (TGA)

For products manufactured in, or sold into New Zealand refer to Medsafe for more information: Medsafe

If you would like some help, or just don’t know where to start we have consultants available to aid with nitrosamine risk assessments.  Click here to fill in a contact form.