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WHO Guidance: GMP in Preventing and Controlling Nitrosamine Contamination in Pharmaceuticals

Earlier this week, the World Health Organization (WHO) released draft guidelines "WHO Good Manufacturing Practices Considerations for the Prevention and Control of Nitrosamine Contamination in Pharmaceutical Products" for comments on how to prevent and control nitrosamine contamination, that are one of the major reasons for cancer.

Nitrosamines is a group or class of compounds that have the chemical structure of a nitroso group bonded to an amine (R1N(-R2)-N=O) and can be found in certain medications and are classified as probable human carcinogens.

The presence of nitrosamines in drug products has raised concerns among regulatory authorities worldwide. This guidance aims to help manufacturers identify and mitigate the risk of nitrosamine contamination in medicines.

Manufacturers of excipients, active pharmaceutical ingredients (APIs), and finished pharmaceutical products are required to comply with the new GMP guideline. Also, the guidance discusses impurities currently causing concern as well as root cause analyses and risk assessments.

New impurities of concern may be identified on an ongoing basis. The following nitrosamine impurities are currently of concern:

  • N-nitrosodimethylamine (NDMA)

  • N-nitrosodiethylamine (NDEA)

  • N-nitrosodiisopropylamine (NDIPA)

  • N-nitroso-N-methyl-4-aminobutanoic acid (NMBA)

  • 1-methyl-4-nitrosopiperazine (MNP)

  • N-nitrosoethylisopropylamine (NEIPA)

  • N-nitrosodibutylamine (NDBA)

To determine if their products are at risk of contamination with nitrosamine impurities, manufacturers should conduct comprehensive risk assessments. The risk assessment should include, but not be limited to, the premises, equipment, materials, synthesis route, production process, interaction between chemicals, excipients, solvents, APIs, and packaging components, as well as its intended use and administration method.

Where manufacturers identify contamination of nitrosamines above acceptable limits, appropriate action should be taken. Risk and impact assessment should be done with root cause determination. Comments on the guidance are being accepted through an online WHO review site and by email. Comments are due by June 9.

Check out this guidance for more detailed information by clicking this LINK.


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